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Heidemarie Rossiter,
Ulrich König,
Caterina Barresi,
Maria Buchberger,
Minoo Ghannadan,
Cheng-Feng Zhang,
Veronika Mlitz,
Ramona Gmeiner,
Supawadee Sukseree,
Dagmar Födinger, Leopold Eckhart,
Erwin Tschachler
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ABSTRACT: BACKGROUND: Cornification of keratinocytes involves the degradation of intracellular constituents which has led to the hypothesis that autophagy plays a role in this process. Mice, in which essential autophagy-related genes such as Atg7 are deleted systemically, die after birth and have not been characterized for potential epidermal defects. OBJECTIVE: This study tested whether autophagy is essential for epidermal barrier formation and function. METHODS: Atg7 was inactivated in epidermal keratinocytes by the Cre-loxP system under the control of the keratin K14 promoter (Atg7Δepi mice). Autophagic activity was detected using the GFP-microtubule-associated protein light chain 3 (GFP-LC3) reporter construct and Western blot analysis of LC3. Epidermal morphology was examined by histological and ultrastructural analyses, and barrier functions were assessed by dye diffusion and water loss assays. RESULTS: Suprabasal epidermal cells of normal mice contained GFP-LC3-labeled autophagosomes and epidermal lysates of these mice showed an excess of lipidated over non-lipidated LC3. These features of active autophagy were efficiently suppressed in Atg7Δepi epidermis. Atg7Δepi mice survived the perinatal period and were apparently healthy. Histologically, their epidermis was inconspicuous and ultrastructural analysis revealed no significant defect in cornification. There was however, an increase in the thickness of corneocytes in the back skin of mutant mice. Nevertheless, resistance to dye penetration into the skin and transepidermal water loss were normal in Atg7Δepi mice. CONCLUSION: This study demonstrates that autophagy is constitutively active in the epidermis but not essential for the barrier function of the skin.
Journal of dermatological science 04/2013; · 3.71 Impact Factor
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ABSTRACT: The skin is exposed to environmental insults such as ultraviolet light which cause oxidative damage to macromolecules. A centerpiece in the defense against oxidative stress is the Nrf2 (Nuclear factor (erythroid-derived-2)-like 2)-mediated transcriptional up-regulation of antioxidant and detoxifying enzymes and the removal of oxidatively damaged material. Autophagy plays an important role for the intra-cellular degradation of damaged proteins and entire organelles but its role in the epidermis has remained elusive. Here we show that both ultraviolet A (UVA) and UVA-oxidized phospholipids induced autophagy in epidermal keratinocytes. Oxidative stressors induced massive accumulation of high molecular weight protein aggregates containing the autophagy adaptor protein p62/SQSTM1 in autophagy-deficient (ATG7 negative) keratinocytes. Strikingly, even in the absence of exogenous stress, the expression of Nrf2 dependent genes was elevated in autophagy-deficient keratinocytes. Furthermore we show that autophagy-deficient cells contained significantly elevated levels of reactive oxidized phospholipids. Thus our data demonstrate that autophagy is crucial for both the degradation of proteins and lipids modified by environmental UV-stress and for limiting Nrf2 activity in keratinocytes. Lipids that promote inflammation and tissue damage due to their reactivity and signaling functions are commonly observed in aged and diseased skin, thus targeting autophagy may be a promising strategy to counteract the damage promoted by excessive lipid oxidation.Journal of Investigative Dermatology accepted article preview online, 22 January 2013; doi:10.1038/jid.2013.26.
Journal of Investigative Dermatology 01/2013; · 6.31 Impact Factor
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ABSTRACT: Autophagy contributes to the homeostasis of many tissues, yet its role in epithelia is incompletely understood. A recent report proposed that Atg5-dependent autophagy in thymic epithelial cells is essential for their function in the negative selection of self-reactive T-cells and, thus, for the suppression of tissue inflammation. Here we crossed mice carrying floxed alleles of the Atg5 gene with mice expressing the Cre recombinase under the control of the keratin K5 promoter to suppress autophagy in all K5-positive epithelia. The efficiency of autophagy abrogation was confirmed by immunoanalyses of LC3, which was converted to the autophagy-associated LC3-II form in normal but not Atg5-deficient cells, and of p62, which accumulated in Atg5-deficient cells. Mice carrying the epithelium-specific deletion of Atg5 showed normal weight gain, absence of tissue inflammation, and a normal morphology of the thymic epithelium. By contrast, autophagy-deficient epithelial cells of the preputial gland showed aberrant eosinophilic staining in histology and premature degradation of nuclear DNA during terminal differentiation. Taken together, the results of this study suggest that autophagy is dispensable for the suppression of autoimmunity by thymic epithelial cells but essential for normal differentiation of the preputial gland in mice.
Biochemical and Biophysical Research Communications 12/2012; · 2.48 Impact Factor
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EMBO Molecular Medicine 03/2012; 4(5):362-3. · 10.33 Impact Factor
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ABSTRACT: Degradation of DNA is involved in key processes maintaining the integrity of the epidermis such as the cornification of keratinocytes, the removal of damaged cells and the defense against potentially harmful microorganisms. Recent studies have characterized some of the molecular mechanisms and physiological functions of DNA degradation in the epidermis. Deoxyribonuclease (DNase)1L2 and TREX2 were identified as epidermis-specific DNases and DNase 2 was shown to be the predominant DNA-degrading enzyme on the surface of the skin. Here we review the latest insights into the DNA catabolism in the skin and discuss open questions pertaining to the molecular biology of epidermal DNA breakdown.
Frontiers in Bioscience 01/2012; 17:2461-75. · 3.52 Impact Factor
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ABSTRACT: The thymic epithelium plays critical roles in the positive and negative selection of T cells. Recently, it was proposed that autophagy in thymic epithelial cells is essential for the induction of T cell tolerance to self antigens and thus for the prevention of autoimmune diseases. Here we have tested this hypothesis using mouse models in which autophagy was blocked specifically in epithelial cells expressing keratin 14 (K14), including the precursor of thymic epithelial cells. While the thymic epithelial cells of mice carrying the floxed Atg7 gene (ATG7 f/f) showed a high level of autophagy, as determined by LC3 Western blot analysis and fluorescence detection of the recombinant green fluorescent protein (GFP)-LC3 reporter protein on autophagosomes, autophagy in the thymic epithelium was efficiently suppressed by deletion of the Atg7 gene using the Cre-loxP system (ATG7 f/f K14-Cre). Suppression of autophagy led to the massive accumulation of p62/sequestosome 1 (SQSTM1) in thymic epithelial cells. However, the structure of the thymic epithelium as well as the organization and the size of the thymus were not altered in mutant mice. The ratio of CD4 to CD8-positive T cells, as well as the frequency of activated (CD69+) CD4 T cells in lymphoid organs, did not differ between mice with autophagy-competent and autophagy-deficient thymic epithelium. Inflammatory infiltrating cells, potentially indicative of autoimmune reactions, were present in the liver, lung, and colon of a similar fraction of ATG7 f/f and ATG7 f/f K14-Cre mice. In contrast to previously reported mice, that had received an autophagy-deficient thymus transplant, ATG7 f/f K14-Cre mice did not suffer from autoimmunity-induced weight loss. In summary, the results of this study suggest that autophagy in the thymic epithelium is dispensable for negative selection of autoreactive T cells.
PLoS ONE 01/2012; 7(6):e38933. · 4.09 Impact Factor
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ABSTRACT: Although mutations in the filaggrin gene (FLG) have been shown to be associated with ichthyosis vulgaris and atopic dermatitis, the function and regulation of filaggrin remain incompletely understood. In this issue, Hoste et al. report that filaggrin is directly cleaved by caspase-14. Acting in concert with other proteases, caspase-14 controls the breakdown of filaggrin to free amino acids and amino acid derivatives that contribute to the hydration and UVB absorption capacity of the stratum corneum. These findings identify a new layer of complexity in the regulation of epidermal barrier function.
Journal of Investigative Dermatology 11/2011; 131(11):2173-5. · 6.31 Impact Factor
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ABSTRACT: Hair fibers are formed by keratinocytes of the hair follicle in a process that involves the breakdown of the nucleus including DNA. Accordingly, DNA can be isolated with high yield from the hair bulb which contains living keratinocytes, whereas it is difficult to prepare from the distal portions of hair fibers and from shed hair. Nevertheless, forensic investigations are successful in a fraction of shed hair samples found at crime scenes. Here, we report that interindividual differences in the completeness of DNA removal from hair corneocytes are major determinants of DNA content and success rates of forensic investigations of hair. Distal hair samples were permeabilized with ammonia and incubated with the DNA-specific dye Hoechst 33258 to label DNA in situ. Residual nuclear DNA was visualized under the fluorescence microscope. Hair from some donors did not contain any stainable nuclei, whereas hair of other donors contained a variable number of DNA-positive nuclear remnants. The number of DNA-containing nuclear remnants per millimeter of hair correlated with the amount of DNA that could be extracted and amplified by quantitative PCR. When individual hairs were investigated, only hairs in which DNA could be labeled in situ gave positive results in short tandem repeat typing. This study reveals that the completeness of DNA degradation during cornification of the hair is a polymorphic trait. Furthermore, our results suggest that in situ labeling of DNA in hair may be useful for predicting the probability of success of forensic analysis of nuclear DNA in shed hair.
Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 04/2011; 126(1):63-70. · 2.59 Impact Factor
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ABSTRACT: The claw of lizards is largely composed of beta-keratins, also referred to as keratin-associated beta-proteins. Recently, we have reported that the genome of the lizard Anolis carolinensis contains alpha keratin genes homologous to hair keratins typical of hairs and claws of mammals. Molecular and immunohistochemical studies demonstrated that two hair keratin homologs named hard acid keratin 1 (HA1) and hard basic keratin 1 (HB1) are expressed in keratinocytes forming the claws of A. carolinensis. Here, we extended the immunocytochemical localization of the novel reptilian keratins to the ultrastructural level. After sectioning, claws were subjected to immunogold labeling using antibodies against HA1, HB1, and, for comparison, beta-keratins. Electron microscopy showed that the randomly organized network of tonofilaments in basal and suprabasal keratinocytes becomes organized in long and parallel bundles of keratin in precorneous layers, resembling cortical cells of hairs. Entering the cornified part of the claw, the elongated corneous cells fuse and accumulate corneous material. HA1 and HB1 are absent in the basal layer and lower spinosus layers of the claw and are expressed in the upper and precorneous layers, including the elongating corneocytes. The labeling for alpha-keratin was loosely associated with filament structures forming the fibrous framework of the claws. The ultrastructural distribution pattern of hard alpha-keratins resembled that of beta-keratins, which is compatible with the hypothesis of an interaction during claw morphogenesis. The data on the ultrastructural localization of hair keratin homologs facilitate a comparison of lizard claws and mammalian hard epidermal appendages containing hair keratins.
Journal of Morphology 03/2011; 272(3):363-70. · 1.54 Impact Factor
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Heinz Fischer,
Sandra Szabo,
Jennifer Scherz,
Karin Jaeger,
Heidemarie Rossiter,
Maria Buchberger,
Minoo Ghannadan,
Marcela Hermann,
Hans-Christian Theussl,
Desmond J Tobin,
Erwin F Wagner,
Erwin Tschachler, Leopold Eckhart
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ABSTRACT: Degradation of nuclear DNA is a hallmark of programmed cell death. Epidermal keratinocytes die in the course of cornification to function as the dead building blocks of the cornified layer of the epidermis, nails, and hair. Here, we investigated the mechanism and physiological function of DNA degradation during cornification in vivo. Targeted deletion of the keratinocyte-specific endonuclease DNase1-like 2 (DNase1L2) in the mouse resulted in the aberrant retention of DNA in hair and nails, as well as in epithelia of the tongue and the esophagus. In contrast to our previous studies in human keratinocytes, ablation of DNase1L2 did not compromise the cornified layer of the epidermis. Quantitative PCRs showed that the amount of nuclear DNA was dramatically increased in both hair and nails, and that mitochondrial DNA was increased in the nails of DNase1L2-deficient mice. The presence of nuclear DNA disturbed the normal arrangement of structural proteins in hair corneocytes and caused a significant decrease in the resistance of hair to mechanical stress. These data identify DNase1L2 as an essential and specific regulator of programmed cell death in skin appendages, and demonstrate that the breakdown of nuclear DNA is crucial for establishing the full mechanical stability of hair.
Journal of Investigative Dermatology 02/2011; 131(6):1208-15. · 6.31 Impact Factor
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ABSTRACT: The cornified layer, the stratum corneum, of the epidermis is an efficient barrier to the passage of genetic material, i.e. nucleic acids. It contains enzymes that degrade RNA and DNA which originate from either the living part of the epidermis or from infectious agents of the environment. However, the molecular identities of these nucleases are only incompletely known at present. Here we performed biochemical and genetic experiments to determine the main DNase activity of the stratum corneum. DNA degradation assays and zymographic analyses identified the acid endonucleases L-DNase II, which is derived from serpinB1, and DNase 2 as candidate DNases of the cornified layer of the epidermis. siRNA-mediated knockdown of serpinB1 in human in vitro skin models and the investigation of mice deficient in serpinB1a demonstrated that serpinB1-derived L-DNase II is dispensable for epidermal DNase activity. By contrast, knockdown of DNase 2, also known as DNase 2a, reduced DNase activity in human in vitro skin models. Moreover, the genetic ablation of DNase 2a in the mouse was associated with the lack of acid DNase activity in the stratum corneum in vivo. The degradation of endogenous DNA in the course of cornification of keratinocytes was not impaired by the absence of DNase 2. Taken together, these data identify DNase 2 as the predominant DNase on the mammalian skin surface and indicate that its activity is primarily targeted to exogenous DNA.
PLoS ONE 01/2011; 6(3):e17581. · 4.09 Impact Factor
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ABSTRACT: Urocanic acid (UCA) is produced by the enzyme histidase and accumulates in the stratum corneum of the epidermis. In this study, we investigated the photoprotective role of endogenous UCA in the murine skin using histidinemic mice, in which the gene encoding histidase is mutated. Histidase was detected by immunohistochemistry in the stratum granulosum and stratum corneum of the normal murine skin but not in the histidinemic skin. The UCA content of the stratum corneum and the UVB absorption capacity of aqueous extracts from the stratum corneum were significantly reduced in histidinemic mice as compared with wild-type mice. When the shaved back skin of adult mice was irradiated with 250 mJ cm(-2) UVB, histidinemic mice accumulated significantly more DNA damage in the form of cyclobutane pyrimidine dimers than did wild-type mice. Furthermore, UVB irradiation induced significantly higher levels of markers of apoptosis in the epidermis of histidinemic mice. Topical application of UCA reversed the UVB-photosensitive phenotype of histidinemic mice and increased UVB photoprotection of wild-type mice. Taken together, these results provide strong evidence for an important contribution of endogenous UCA to the protection of the epidermis against the damaging effects of UVB radiation.
Journal of Investigative Dermatology 01/2011; 131(1):188-94. · 6.31 Impact Factor
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ABSTRACT: We have recently shown that homologs of mammalian hair keratins are expressed in the claws of the green anole lizard, Anolis carolinensis. To test whether reptilian hair keratin homologs are functionally associated with claws, we investigated the conservation of the prototypical reptilian hair keratin homolog, hard acidic keratin 1 (HA1), in representative species from all main clades of reptiles. A complete cDNA of HA1 was cloned from the claw-forming epidermis of the lacertid lizard Podarcis sicula, and partial HA1 gene sequences could be amplified from genomic DNA of tuatara, lizards, gekkos, turtles, and crocodiles. In contrast, the HA1 gene of the limbless slow worm, Anguis fragilis, and of two species of turtles contained at least one deleterious mutation. Moreover, an HA1 gene was undetectable in the softshell turtle, snakes, and birds. Mapping the presence and absence of HA1 onto the phylogenetic tree of sauropsids suggested that the HA1 gene has been lost independently in several lineages of reptiles. The species distribution of HA1 is compatible with the hypothesis of a primary function of HA1 in claws but also shows that the formation of reptilian claws does not strictly depend on this keratin.
Journal of Molecular Evolution 12/2010; 72(3):265-73. · 2.27 Impact Factor
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ABSTRACT: Antimicrobial peptides (AMPs) have a central role in the innate immune system of the skin. Epidermal keratinocytes (KCs) express numerous such peptides either constitutively or in response to exposure to microbial compounds. Here, we investigated the regulation of S100A8 (calgranulin A) and S100A9 (calgranulin B), which form an antimicrobial heterodimeric complex also known as calprotectin, in KCs. Culture supernatants of gram-negative bacteria, but not of gram-positive bacteria nor of the yeast Candida albicans, triggered the expression of S100A8 and S100A9. To identify pathogen-associated molecular patterns (PAMPs) responsible for the upregulation of S100A8 and S100A9, KCs were stimulated with ligands for Toll-like receptors (TLRs). Quantitative real-time PCR (qRT-PCR) analysis revealed that the TLR5 ligand flagellin increased the mRNA expression of both S100A8 and S100A9. Supernatant from wild-type (WT) Escherichia coli, but not from a flagellin-deficient E. coli strain (ΔFliC), induced S100A8 and S100A9 protein production in KCs. Moreover, small interfering RNA-mediated knockdown of TLR5 expression suppressed the ability of KCs to upregulate S100A8 and S100A9 mRNA expression in response to E. coli supernatant. Like in cell culture, stimulation of human skin explants with E. coli induced the expression of S100A8 and S100A9. Our data suggest that bacterial flagellin induces the upregulation of S100A8/S100A9 via a TLR5-dependent mechanism in epidermal KCs.
Journal of Investigative Dermatology 10/2010; 130(10):2423-30. · 6.31 Impact Factor
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ABSTRACT: Retinoids are regulators of keratinocyte differentiation in the epidermis and important therapeutics in dermatology. The formation of the most active retinoid, all-trans-retinoic acid (RA) by oxidation of retinal is catalyzed by aldehyde dehydrogenases (ALDH), of which ALDH1A3 has been shown to be most efficient. Here we investigated the expression of ALDH1A3 in epidermal cultures. Three alternatively spliced mRNAs of ALDH1A3 were detected in skin cultures with the conventionally spliced mRNA being predominant. Among a panel of ALDH genes, only ALDH1A3 was upregulated by RA in primary keratinocytes. RA increased the expression of ALDH1A3 also in organotypic human skin cultures and in an epidermal explant in vitro whereas no upregulation was detected in dermal fibroblasts and HeLa cells. Our results indicate that the regulation of the retinoic acid metabolism in the epidermis involves transcriptional activation of ALDH1A3, possibly representing a positive feedback loop, which enhances the effect of exogenous RA.
Biochemical and Biophysical Research Communications 09/2010; 400(2):207-11. · 2.48 Impact Factor
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Michael Mildner,
Jiang Jin, Leopold Eckhart,
Sanja Kezic,
Florian Gruber,
Caterina Barresi,
Caroline Stremnitzer,
Maria Buchberger,
Veronika Mlitz,
Claudia Ballaun,
Barbara Sterniczky,
Dagmar F|[ouml]|dinger,
Erwin Tschachler
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ABSTRACT: Loss-of-function mutations in the filaggrin gene are associated with ichthyosis vulgaris and atopic dermatitis. To investigate the impact of filaggrin deficiency on the skin barrier, filaggrin expression was knocked down by small interfering RNA (siRNA) technology in an organotypic skin model in vitro. Three different siRNAs each efficiently suppressed the expression of profilaggrin and the formation of mature filaggrin. Electron microscopy revealed that keratohyalin granules were reduced in number and size and lamellar body formation was disturbed. Expression of keratinocyte differentiation markers and the composition of lipids appeared normal in filaggrin-deficient models. The absence of filaggrin did not render keratins 1, 2, and 10 more susceptible to extraction by urea, arguing against a defect in aggregation. Despite grossly normal stratum corneum morphology, filaggrin-deficient skin models showed a disturbed diffusion barrier function in a dye penetration assay. Moreover, lack of filaggrin led to a reduction in the concentration of urocanic acid, and sensitized the organotypic skin to UVB-induced apoptosis. This study thus demonstrates that knockdown of filaggrin expression in an organotypic skin model reproduces epidermal alterations caused by filaggrin mutations in vivo. In addition, our results challenge the role of filaggrin in intermediate filament aggregation and establish a link between filaggrin and endogenous UVB protection.Abbreviations: KC, keratinocyte; siRNA, small interfering RNA; UCA, urocanic acid
Journal of Investigative Dermatology 05/2010; 130(9):2286-2294. · 6.31 Impact Factor
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Michael Mildner,
Jiang Jin, Leopold Eckhart,
Sanja Kezic,
Florian Gruber,
Caterina Barresi,
Caroline Stremnitzer,
Maria Buchberger,
Veronika Mlitz,
Claudia Ballaun,
Barbara Sterniczky,
Dagmar Födinger,
Erwin Tschachler
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ABSTRACT: Loss-of-function mutations in the filaggrin gene are associated with ichthyosis vulgaris and atopic dermatitis. To investigate the impact of filaggrin deficiency on the skin barrier, filaggrin expression was knocked down by small interfering RNA (siRNA) technology in an organotypic skin model in vitro. Three different siRNAs each efficiently suppressed the expression of profilaggrin and the formation of mature filaggrin. Electron microscopy revealed that keratohyalin granules were reduced in number and size and lamellar body formation was disturbed. Expression of keratinocyte differentiation markers and the composition of lipids appeared normal in filaggrin-deficient models. The absence of filaggrin did not render keratins 1, 2, and 10 more susceptible to extraction by urea, arguing against a defect in aggregation. Despite grossly normal stratum corneum morphology, filaggrin-deficient skin models showed a disturbed diffusion barrier function in a dye penetration assay. Moreover, lack of filaggrin led to a reduction in the concentration of urocanic acid, and sensitized the organotypic skin to UVB-induced apoptosis. This study thus demonstrates that knockdown of filaggrin expression in an organotypic skin model reproduces epidermal alterations caused by filaggrin mutations in vivo. In addition, our results challenge the role of filaggrin in intermediate filament aggregation and establish a link between filaggrin and endogenous UVB protection.
Journal of Investigative Dermatology 05/2010; 130(9):2286-94. · 6.31 Impact Factor
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Journal of Investigative Dermatology 04/2010; 130(8):2141-4. · 6.31 Impact Factor
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Matthias Hackl,
Stefan Brunner,
Klaus Fortschegger,
Carina Schreiner,
Lucia Micutkova,
Christoph Mück,
Gerhard T Laschober,
Günter Lepperdinger,
Natalie Sampson,
Peter Berger, [......],
Erwin Tschachler,
Andrea Trost,
Johann W Bauer,
Christine Papak,
Zlatko Trajanoski,
Marcel Scheideler,
Regina Grillari-Voglauer,
Beatrix Grubeck-Loebenstein,
Pidder Jansen-Dürr,
Johannes Grillari
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ABSTRACT: Aging is a multifactorial process where deterioration of body functions is driven by stochastic damage while counteracted by distinct genetically encoded repair systems. To better understand the genetic component of aging, many studies have addressed the gene and protein expression profiles of various aging model systems engaging different organisms from yeast to human. The recently identified small non-coding miRNAs are potent post-transcriptional regulators that can modify the expression of up to several hundred target genes per single miRNA, similar to transcription factors. Increasing evidence shows that miRNAs contribute to the regulation of most if not all important physiological processes, including aging. However, so far the contribution of miRNAs to age-related and senescence-related changes in gene expression remains elusive. To address this question, we have selected four replicative cell aging models including endothelial cells, replicated CD8(+) T cells, renal proximal tubular epithelial cells, and skin fibroblasts. Further included were three organismal aging models including foreskin, mesenchymal stem cells, and CD8(+) T cell populations from old and young donors. Using locked nucleic acid-based miRNA microarrays, we identified four commonly regulated miRNAs, miR-17 down-regulated in all seven; miR-19b and miR-20a, down-regulated in six models; and miR-106a down-regulated in five models. Decrease in these miRNAs correlated with increased transcript levels of some established target genes, especially the cdk inhibitor p21/CDKN1A. These results establish miRNAs as novel markers of cell aging in humans.
Aging cell 04/2010; 9(2):291-6. · 7.55 Impact Factor
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ABSTRACT: Digital end organs composed of hard, modified epidermis, generally referred to as claws, are present in mammals and reptiles as well as in several non-amniote taxa such as clawed salamanders and frogs, including Xenopus laevis. So far, only the claws and nails of mammals have been characterized extensively and the question of whether claws were present in the common ancestor of all extant tetrapods is as yet unresolved. To provide a basis for comparisons between amniote and non-amniote claws, we investigated the development, growth and ultrastructure of the epidermal component of the claws of X. laevis. Histological examination of developing claws of X. laevis shows that claw formation is initiated at the tip of the toe by the appearance of superficial cornified cells that are dark brown. Subsequent accumulation of new, proximally extended claw sheath corneocyte layers increases the length of the claw. Histological studies of adult claws show that proliferation of cornifying claw sheath cells occurs along the entire length of the claw-forming epidermis. Living epidermal cells that are converting into the cornified claw sheath corneocytes undergo a form of programmed cell death that is accompanied by degradation of nuclear DNA. Subsequently, the cytoplasm and the nuclear remnants acquire a brown colour by an as-yet unknown mechanism that is likely homologous to the colouration mechanism that occurs in other hard, cornified structures of amphibians such as nuptial pads and tadpole beaks. Transmission electron microscopy revealed that the cornified claw sheath consists of parallel layers of corneocytes with interdigitations being confined to intra-layer contacts and a cementing substance filling the intercorneocyte spaces. Together with recent reports that showed the main molecular components of amniote claws are absent in Xenopus, our data support the hypothesis that claws of amphibians likely represent clade-specific innovations, non-homologous to amniote claws.
Journal of Anatomy 05/2009; 214(4):607-19. · 2.37 Impact Factor
