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ABSTRACT: Vascular endothelial growth factor (VEGF) promotes angiogenesis and plays important roles both in physiological and pathological conditions. VEGF receptors (VEGFRs) are high-affinity receptors for VEGF and are originally considered specific to endothelial cells. We previously reported that VEGFRs were also constitutively expressed in normal human keratinocytes and overexpressed in psoriatic epidermis. In addition, UVB can activate VEGFRs in normal keratinocytes, and the activated VEGFR-2 signaling is involved in the pro-survival mechanism. Here, we show that VEGFRs were also upregulated and activated by UVA in normal human keratinocytes via PKC, and interestingly, both the activated VEGFR-1 and VEGFR-2 protected against UVA-induced cell death. As VEGFRs were over-expressed in psoriatic epidermis, we further investigated whether narrowband UVB (NB-UVB) phototherapy or topical halomethasone monohydrate 0.05% cream could affect their expression. Surprisingly, the over-expressed VEGFRs in psoriatic epidermis were significantly attenuated by both treatments. During NB-UVB therapy, VEGFRs declined first in the basal, and then gradually in the upper psoriatic epidermis. VEGFRs were activated in psoriatic epidermis, their activation was enhanced by NB-UVB, but turned undetectable after whole therapy. This process was quite different from that by halomethasone, in which VEGFRs and phospho-VEGFRs decreased in a gradual, homogeneous manner. Our findings further suggest that UV-induced activation of VEGFRs serves as a pro-survival signal for keratinocytes. In addition, VEGFRs may be involved in the pathological process of psoriasis, and UV phototherapy is effective for psoriasis by directly modulating the expression of VEGFRs.
PLoS ONE 01/2013; 8(1):e55463. · 4.09 Impact Factor
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ABSTRACT: Artemis phosphorylation at serine 516 (Ser516) has important regulatory functions in the repair of radiation-induced DNA damage, V(D)J recombination, p53-dependent apoptosis and cell cycle control. Accordingly, Artemis mutations can lead to Omenn syndrome, which is associated with human radiosensitive severe combined immunodeficiency syndrome and alopecia. In this study, we investigated the expression of Ser516 phosphorylation of Artemis in the epidermis and epidermal appendages in normal human scalp skin. Immunofluorescence analysis revealed Ser516 phosphorylation of Artemis in the upper and middle portion of anagen hair follicle [including outer root sheath (ORS), inner root sheath but not stratum basale], hair matrix, sebaceous glands (secretory and ductal portions), eccrine sweat glands (secretory and ductal portions) and epidermis (stratum basale and stratum granulosum), respectively. Artemis phosphorylation at Ser516 was most prominent in ORS keratinocytes. Therefore, we suggest that phosphorylation of Artemis at Ser516 could be involved in regulation of human epidermal appendages.
Experimental Dermatology 11/2012; 21(11):881-3. · 3.54 Impact Factor
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Medical Hypotheses 07/2012; 79(4):554. · 1.39 Impact Factor
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ABSTRACT: Vascular endothelial growth factor (VEGF) is a key regulator of physiological and pathological angiogenesis. The biological effects of VEGF are mediated by receptor tyrosine kinases. VEGF receptor-2, the primary receptor for VEGF, is thought to mediate most functional effects. In this study, we examined the expression and roles of VEGF receptor-2 on human outer root sheath cells (ORS). The expression of VEGFR-2 was determined at mRNA and protein levels by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Localization of VEGFR-2 in ORS cells was detected by immunofluorescence. The effect of VEGF on ORS cell proliferation was determined by MTT assays. Our data showed the expression of VEGFR-2 on ORS cells at both mRNA and protein levels. Immunostaining for VEGFR-2 demonstrated strong signal on cultured ORS cells. Exogenous VEGF(165) stimulated proliferation of ORS cells and upregulated expression of VEGFR-2 in a dose-dependent manner. Moreover, VEGF(165) induced phosphorylation of VEGFR-2, PLC-γ1, PKC-α, MEK, and p44/42 MAPK (ERK1/2) in a time-dependent manner. Taken together, human ORS cells express functional VEGF receptor-2 and exogenous VEGF(165) upregulates expression of VEGFR-2 and stimulates proliferation of ORS cells via VEGFR-2 mediated ERK signaling pathway.
Molecular Biology Reports 06/2012; 39(9):8687-94. · 2.93 Impact Factor
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ABSTRACT: Vascular endothelial growth factor (VEGF) is one of the strongest regulators of physiological and pathological angiogenesis. VEGF receptor 2 (VEGFR-2), the primary receptor for VEGF, is thought to mediate major functional effects of VEGF. Previously, we have localized both VEGF and VEGFR-2 in human hair follicles. In this study, we further defined the expression and roles of VEGFR-2 on human hair follicle dermal papilla (DP) cells. The expression of VEGFR-2 on DP cells was examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis separately, and localization of VEGFR-2 was defined by immunofluorescence. The effect of VEGF on DP cells was analyzed by MTT assays and specific inhibitors. Finally, the role of VEGF involved in the signaling pathways was investigated by Western blot. RT-PCR and Western blot analysis demonstrated the expression of VEGFR-2 on DP cells. Immunostaining for VEGFR-2 showed strong signal on cultured human DP cells in vitro. Exogenous VEGF(165) stimulated proliferation of DP cells in a dose-dependent manner. Furthermore, this stimulation was blocked by a VEGFR-2 neutralizing antibody (MAB3571) and an ERK inhibitor (PD98059). VEGF(165)-induced phosphorylation of ERK1/2 was abolished by MAB3571 and PD98059, while the phosphorylation of p38, JNK and AKT were not changed by VEGF(165). Taken together, VEGFR-2 is expressed on primary human hair follicle DP cells and VEGF induces proliferation of DP cells through VEGFR-2/ERK pathway, but not p38, JNK or AKT signaling.
Experimental Cell Research 05/2012; 318(14):1633-40. · 3.58 Impact Factor
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ABSTRACT: Artemis has been implicated in having a role in NHEJ, and it is also a multifunctional protein. Previous studies have found Omenn syndrome-like phenotype due to Artemis mutations and associated with alopecia. As Artemis phosphorylation in its c-terminus including Serine516 is prerequisite for the Artemis endonuclease reaction, we postulate that Artemis (Serine516) may be expressed in hair follicle and relate to hair cycling. In this study, hair growth in C57BL/6 mice was induced by plucking the telogen hair on the back. Expression of Artemis (Serine516) in hair follicles during the hair growth cycle was evaluated by immunofluorescence using cryosections and a specific polyclonal anti-Artemis (Serine516) immunoglobulin G (IgG) antibody. It was detected in germ cells, cap, and club hair adjoining the epidermis in telogen. In anagen II, intense staining for Artemis (Serine516) was found in the whole interfollicular epidermis, and in strand keratinocytes. In anagen IV, intense staining for Artemis (Serine516) was detected in basal cells and upper of outer root sheath (ORS) and inner root sheath (IRS). But only upper ORS and lower medulla were stained positive in anagen VI. Upper ORS and lower cortex were positively stained with Artemis (Serine516) in catagen. Based on the phenomenon that the expression of Artemis (Serine516) in mid-anagen and mature anagen was stronger than that in telogen and catagen, we suggest it may take roles in induced growth of mouse hair.
Archives for Dermatological Research 04/2012; 304(4):319-24. · 2.28 Impact Factor
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ABSTRACT: Mounting evidence indicates that signaling via VEGF receptors (VEGFRs) extends beyond blood vessel formation. Recently, VEGFRs are also found to be constitutively expressed in keratinocytes and epidermal appendages. Here, we show that the expression of VEGFRs (including VEGFR-1, VEGFR-2, and NRP-1) was significantly enhanced by moderate dose of ultraviolet B (UVB) in normal human keratinocytes and epidermis. The elevated expression of VEGFRs by UVB was independent of autocrine stimulation by their natural ligand, VEGF, but mainly mediated through hypoxia and oxidative stress. Moderate dose UVB also promoted tyrosine phosphorylation of VEGFR-1 and VEGFR-2, this effect was again VEGF independent. Both α and δ isoforms of protein kinase C (PKC) were required for UVB-induced phosphorylation of VEGFR-1, but only the δ isoform was required for VEGFR-2 phosphorylation. The phosphorylation of VEGFRs or isoforms of PKC was completely inhibited by PP2, a specific inhibitor for Src family kinases (SFKs), indicating that SFKs are upstream of PKC and VEGFRs. Moderate dose UVB-induced VEGF exerted an anti-apoptotic effect for keratinocytes, whereas high dose UVB-induced VEGF played as an inflammatory factor. Of note, neutralization of VEGFR-2 but not VEGFR-1 exacerbated UVB-induced cell death and reduced survival of keratinocytes. Furthermore, VEGFR-2 neutralization inhibited the activation of ERK1/2 and Akt by UVB, suggesting that VEGFR-2 signaling was involved in the pro-survival mechanism via ERK1/2 and PI3-K/Akt pathway. Taken together, we demonstrate for the first time that VEGFR-2 signaling is activated and promotes survival of keratinocytes under moderate dose of UVB irradiation.
The international journal of biochemistry & cell biology 11/2011; 44(1):246-56. · 4.89 Impact Factor
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ABSTRACT: To investigate the possibility of hair follicle reformation induced by dermal papilla cells in vivo and in vitro. Dermal papilla cells, dermal sheath cells obtained from human scalp skin by enzyme digestion were mixed with collagen to form mesenchymal cell-populated collagen gels. Superior and inferior epithelial cells and bulb matrical cells were then cultured on these gels by organotypic culture to recombine bilayer artificial skins. Dermal papilla cells and outer root sheath keratinocytes were mingled together and transplanted under subcutaneous tissue of the dorsal skin of nude mice. The results of histologic examination was observed with HE stain. These recombinants by organotypic culture all reformed bilayer structure like nature skin. Hair follicle-like structure reformation was found in dermal sheath cell-populated collagen gel when combined with superior or inferior epithelial cells. Dermal papilla cells also induced superior and inferior epithelial cells to form hair follicle on nude mice. Low passage dermal papilla cells mixed with hair follicle epithelial cells reformed many typical hair follicle structures and produced hair fibres after transplantation on nude mice. The dermal part of hair follicle, such as dermal papilla cells and dermal sheath cells, has the ability to induce hair follicle formation by interaction with the epithelial cells of hair follicle.
Archives for Dermatological Research 10/2006; 298(4):183-90. · 2.28 Impact Factor
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ABSTRACT: To investigate the effect of water soluble extracts of traditional Chinese herbs on growth of mouse hair follicles and hair bulb cells in vitro.
Mouse hair follicles and hair bulb cells were cultured in Williams E medium with (experimental groups) or without (control group) water soluble extracts of Chinese herbs; the experimental group was further divided into mixture and single herb groups. Hair growth was observed by microscopy and growth activity of hair bulb cells was detected by MTT colorimetric assay.
On day 7 of culture, the hair growth in the mixture groups was faster than that in the control group (P<0.05). On day 3 and 5 of culture, the cell growth activity in the mixture groups was greater than that in the control group (P<0.05). While the hair growth and the cell growth activity between the single herb groups and the control group were not significantly different.
The water soluble extracts of mixed traditional Chinese medicines can promote the growth of mouse hair in vitro and stimulate the proliferation of hair bulb cells; while those of the single traditional Chinese herb have no effect.
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 07/2006; 35(4):435-9.
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Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 08/2004; 33(4):370-4.
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ABSTRACT: To observe the skin regeneration after hair follicle bulb cells were implanted into collagen/chitosan porous scaffolds in vitro.
The cultured dorsal hair follicle bulb cells of 4d-old C57BL/6J mice were implanted into collagen/chitosan porous scaffolds in vitro. The skin regeneration was observed.
The skin-like structure was formed on the collagen/chitosan porous scaffolds where were cultured the hair follicle bulb cells before 4th passages.
The skin-like structure is generated in vitro when early passages of cultured hair bulb cells are implanted into collagen/chitosan porous scaffolds.
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 08/2004; 33(4):281-6.
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Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 08/2004; 33(4):277-80.
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ABSTRACT: To observe the hair follicle regeneration after implantation of hair follicle cells into the subcutis of nude mice.
The cultured hair papilla cells,dermal sheath cells and fibroblast of human scalp were mixed with the cells of hair follicle epithelium in different ratio, and then implanted into the subcutis of nude mice. The regeneration of hair follicle was observed.
The hair follicle-like structure was formed in cluster where the cultured hair follicle epithelium cells were mixed with hair papilla cells. But no hair follicles were formed where the hair follicle epithelium was implanted with dermal sheath cells or fibroblasts.
The hair follicle-like structure is generated in vivo when the mixed cells of early passages cultured hair papilla cells with hair follicle epithelium are implanted into the subcutis of nude mice.
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 08/2004; 33(4):287-9.
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ABSTRACT: To investigate the protective effects of minocycline against hair follicle damage induced by cytosine arabinoside (Ara-c).
An in vitro organ culture of mouse vibrissa follicles was used and different concentrations of Ara-c and minocycline were added in the culture media. The total growth length, growth speed and growth period of hair were observed with invert microscopy and the survival of hair bulb cells was measured by MTT method.
Minocycline (0.3 x 10(-6) approximately 10(-5) mol/L) improved hair follicle total growth length, growth speed and hair growth period and also improved survival of hair bulb cells in vitro organ culture, which were inhibited by Ara-c.
Minocycline can protect hair follicle directly from damage induced by Ara-c.
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 08/2004; 33(4):290-5.
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ABSTRACT: To investigate the expression of bFGF, ET-1 and SCF in different passages of cultured dermal papilla cells (DPC), and their possible effect on biological behaviour of DPC.
The expression of bFGF, ET-1 and SCF in different passages of cultured DPC was detected by immunocytochemistry and in situ hybridization.
The expression of ET-1 and SCF in early passages of cultured DPC was stronger, but became negative in late passages (>6 passages). The stronger the expression of ET-1 and SCF in DPC, the higher ability of DPC to induce hair follicle regeneration.
The expression strength of ET-1 and SCF is related to the ability of DPC inducing hair follicle regeneration.
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 08/2004; 33(4):296-9.
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ABSTRACT: To investigate the effects of rat tail collagen, hair follicle dermal papilla cells and hair follicle epithelium cells on collagen gel contraction in organotypic culture.
The hair follicle organotypic culture was prepared with different concentrations of rat tail collagen, different number of dermal papilla cells and hair follicle epithelium cells in DMEM medium, after cultured for 10 days the diameter of collagen gel was measured.
The concentration of rat tail collagen, hair follicle dermal papilla cells and hair follicle epithelium cells significantly influenced on collagen gel contraction in organotypic culture (P<0.01). The contraction of collagen gel was negatively related to the concentration of rat tail collagen, while the concentration of dermal papilla cells and hair follicle epithelium cells was positively related to the contraction of collagen gel.
The key factor influencing collagen gel contraction in organotypic culture is the concentration of rat tail collagen, hair follicle dermal papilla cells and hair follicle epithelium cells.
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 09/2003; 32(4):323-6.
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ABSTRACT: Round and oval skin wounds, like facial pigmented nevi after excision, are traditionally sutured linearly for closure, leaving significant scars, which greatly influences their appearance.
This article provides an overview of our experience using intradermal purse-string suture for round and oval defects in the faciocervical region to ascertain whether purse-string suture closure for such defects can result in good functional and cosmetic outcomes.
We present 63 cases with different skin lesions in the faciocervical area. The defects of the lesions after excision were closed using intradermal purse-string suture. The wounds showed good final healing without obvious adverse events postoperatively. The result of scar assessment using the Vancouver Scar Scale was satisfying, with a total score of only 1.11. The final cosmetic appearance of the healed wounds seemed to be excellent and acceptable as they were always smaller than the original defects, with minimal scarring.
Purse-string suture enabled us to repair small, circular wounds easily after excision of skin lesions. It is an excellent alternative to other reconstructions and a rapid, simple method to close skin defects with minimal scarring, achieving an excellent long-term cosmetic and functional outcome.
Journal of Cutaneous Maedicine and Surgery 16(1):11-7. · 0.98 Impact Factor
