M Seiberg's research while affiliated with University of Rochester Medical Center and other places
Publications (35)
Solar lentigines (SLs, "age spots") are hyperpigmented lesions which are induced by sun exposure and are associated with aging. Histologically, SLs exhibit melanocyte hyperplasia, epidermal finger-like protrusion (rete ridges), and pigment accumulation in the epidermal basal layer. While SLs are benign in nature, reducing the visibility of such les...
Synopsis Dermal elastic fibres are extracellular matrix protein complexes produced by fibroblasts and involved in skin elasticity. Elastin fibres decrease with age as a result of reduced synthesis and increased degradation, resulting in skin sagging and reduced skin elasticity. In this study, we show that retinol (ROL), known to enhance dermal coll...
Treatment of female SKH-1 hairless mice with ultraviolet B light twice a week for 20 weeks resulted in a population of tumor-free mice with a high risk of developing skin tumors during the next several months in the absence of additional UVB treatment (high risk mice). Topical applications of non-denatured soymilk but not heat-denatured soymilk onc...
The production and distribution of melanin in the epidermis defines skin color. Melanin is synthesized in melanocytes and is then transferred into keratinocytes via the melanocytes' dendrites. The protease-activated receptor-2 (PAR-2), expressed on keratinocytes but not on melanocytes, induces keratinocyte phagocytosis and melanosome uptake. Activa...
The microphthalmia-associated transcription factor is implicated in melanocyte development and in the regulation of melanogenesis. Microphthalmia-associated transcription factor is thought to bind to the M-box promoter elements of tyrosinase, tyrosinase-related protein-1 and dopachrome tautomerase/tyrosinase-related protein-2 and transactivate thes...
We have recently shown that soybean-derived serine protease inhibitors and soybean extracts alter skin pigmentation, suggesting that soymilk could be used as a natural alternative to skin lightening. The present studies were initiated to examine the possible effect of STI, BBI and soymilk on hair pigmentation. Interestingly, these agents were found...
Previous studies have shown that the protease-activated receptor 2 is involved in skin pigmentation through increased phagocytosis of melanosomes by keratinocytes. Ultraviolet irradiation is a potent stimulus for melanosome transfer. We show that protease-activated receptor 2 expression in human skin is upregulated by ultraviolet irradiation. Subje...
The epidermal-melanin unit is composed of one melanocyte and approximately 36 neighboring keratinocytes, working in synchrony to produce and distribute melanin. Melanin is synthesized in melanosomes, transferred to the dendrite tips, and translocated into keratinocytes, forming caps over the keratinocyte nuclei. The molecular and cellular mechanism...
The protease-activated receptor 2, expressed on keratinocytes but not on melanocytes, has been ascribed functional importance in the regulation of pigmentation by phagocytosis of melanosomes. Inhibition of protease-activated receptor 2 activation by synthetic serine protease inhibitors requires keratinocyte-melanocyte contact and results in depigme...
The protease-activated receptor-2 (PAR-2) belongs to the family of seven transmembrane domain receptors, which are activated by the specific enzymatic cleavage of their extracellular amino termini. Synthetic peptides corresponding to the tethered ligand domain (SLIGRL in mouse, SLIGKV in human) can activate PAR-2 without the need for receptor cleav...
The chemical basis of melanogenesis is well documented, but the mechanism of melanosome transfer and the regulation of pigmentation by keratinocyte–melanocyte interactions are not well understood. Therefore we examined the effects of serine protease inhibitors on skin pigmentation and found that the protease-activated receptor 2, expressed on kerat...
Close association exists between melanocytes, the pigment melanin-producing cells in the body, and their neighboring keratinocytes. Keratinocytes are the pigment recipients and skin pigmentation is the result of this interaction. While the chemical basis of melanin production (melanogenesis) is well documented, the molecular mechanism of melanosome...
A number of diverse in vitro model systems have been employed for the prediction of irritation potential of test articles. Monolayer systems have proven to be useful for preliminary screening but are not always capable of distinguishing mild effects or adaptable to fully formulated product. Three-dimensional reconstructed skin equivalents integrate...
Acne vulgaris is the result of multifactorial disorders of the pilosebaceous duct. The initial lesion is believed to be hyper-keratinization of the infundibulum. The Rhino mouse has been used as an experimental acne model system for screening anti-keratinizing and comedolytic agents. Using this system we show that trypsin could induce desquamation...
Programmed cell death is a controlled process that leads to the elimination of single cells via apoptosis. Programmed cell death is fundamental to development, morphogenesis, and homeostasis. Proteases play a major role in the death process. We have previously shown that a serine protease, secreted by a keratinocyte cell line, can induce apoptosis...
Thrombin receptor activation was explored in human epidermal keratinocytes and human dermal fibroblasts, cells that are actively involved in skin tissue repair. The effects of thrombin, trypsin, and the receptor agonist peptides SFLLRN and TFRIFD were assessed in inositolphospholipid hydrolysis and calcium mobilization studies. Thrombin and SFLLRN...
The epidermal keratinocyte cell line Pam212 undergoes spontaneous apoptosis in culture, providing an in vitro model for the early steps of epidermal differentiation. Pam212 cells exhibit characteristics of basal keratinocytes, committed for the transition to the spinous layer of the epidermis. Bcl-2 can regulate the differentiation of these cells b...
Programmed cell death is a controlled process that leads to the elimination of single cells via apoptosis, a mode of cell death with a characteristic morphology. During epidermal differentiation, keratinocytes migrate outward to become terminally differentiated cornified cells in a process involving programmed cell death pathway(s) and apoptosis. T...
Clusterin/TRPM-2 is a sulfated glycoprotein that is expressed in many tissues. Independently cloned and isolated by several laboratories, it bears many names, and has been shown to be involved in many processes. These include cell-cell adhesion and aggregation, inhibition of complement cytolysis, programmed cell death and apoptosis, tissue remodeli...
Programmed cell death is central to hair biology, as the hair follicle undergoes cycles of growth (anagen), regression (catagen), and rest (telogen). During catagen, the hair follicle shortens via a pathway of programmed cell death and apoptosis. The molecular mechanisms involved in this process have not been elucidated yet. Using reverse transcrip...
The hair follicle undergoes a cycle of growing, regressing, and resting phases (anagen, catagen, telogen, respectively). As the follicle enters catagen, the cells of the lower, cycling portion undergo a process of controlled cell death (apoptosis). Understanding the mechanism of apoptosis in the follicle should give insight into one of the control...
In this review we tabulated molecules which have been experimentally identified to be associated with, or play a role in, hair follicle growth. While compiling these data we were impressed by the fact that this field is only now beginning to be developed in terms of molecular analysis. Ironically, hair was used in some of the earliest molecular app...
Citations
... [90,[97][98][99][100][101][102] This likely occurs through increased actin dynamics. [103][104][105] This is of critical importance given that the racial origin of keratinocytes determines the pattern of melanosome transfer regardless of the racial origin of ...
... As a consequence, there has been great interest in using the selective properties of enzymes and, thus, proteases have been examined for effectiveness in a number of such topical applications, including animal models of acne vulgaris, wound healing, epidermal ablation, and debridement of necrotic ulcers. Trypsin demonstrated antiaging properties and a comedolytic effect (i.e., opening up of clogged pores and lysis of comedones [hard plugs of keratin and sebum within hair follicles]) in a murine model of acne [11]. The principle physiological change that leads to acne vulgaris is the process of a sebaceous follicle transforming to a comedone via hypercornification and hyper-keratinization of the infundibulum (i.e., the funnel in which the hair follicle grows). ...
... PAM212 cells (22) are an immortalized mouse keratinocyte cell line and were grown in RPMI 1640 supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin (Sigma Chemical Corporation, St. Louis, MO). ...
... Chronic exposure to the sun is the main reason which leads to the overproduction of melanin. Tyrosinase is the crucial enzyme in the production of melanin [1][2][3]. The enzyme tyrosinase (monophenol; oxidoreductase; polyphenol oxidase, PPO; dihydroxy-L-phenylalanin) is a copper-containing enzyme belongs to the oxidase superfamily. ...
... To illustrate the molecular mechanisms of controlling WFD, the expression profiles of different stage of fetal and adult sheep skin have also been generated by sequencing of expressed sequence tags (ESTs) and cDNA microarray [19,20]. However, the size of DP and matrix in mammals is also markedly influenced by genetic [10,11,21], physiological [13], nutrition [22], hormones [12] during the anagen phase of the hair cycle. Up to now, there are no studies on the molecular mechanisms of controlling WFD during the anagen phase, and the genes specifically controlling WFD remain elusive [23]. ...
... During the anagen phase, the FMs synthesize the pigment melanin that will be transferred in the melanosomes to the adjacent keratinocytes, also known as hair progenitors cells, that will be giving arise to the hair shafts (Nishimura et al., 2002;Lin and Fisher, 2007). The melanin synthesis is reduced starting in the catagen phase and be completely absent during the telogen phase, as the lower third of the HF, including the bulb region where the FMs are located, dies through apoptosis (Seiberg et al., 1995;Slominski, 2004;Nishimura, 2011). Therefore, the life of FMs is totally linked with the hair growth cycle, as they disappear when the HFs regress and reappear during the growing phase of the HFs (Steingrímsson et al., 2005;Nishimura, 2011). ...
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... 1. TGM2, STAT2, FGFR2, ILR3RA, CLU, and IGFBP4 were all identiWed as downregulated genes at 24 h compared to submerged cells. Clusterin or CLU expression is known to be diVerentially regulated in skin, and the functions of this gene include cell–cell adhesion and aggregation, inhibition of complement cytolysis, programmed cell death and apoptosis, tissue remodeling, and terminal diVerentiation (Seiberg and Marthinuss 1995). Apoptosis related genes that are found to be up-regulated are listed inTable 1. ...
... On the vascular endothelium and on monocytes, co-expression of PARs and TF drives PAR-2 activation by the TF-FVIIa-FXa complex [46,47], triggering intracellular calcium release, von Willebrand factor release and exposure of P-selectin. Notably, also human keratinocytes express PAR-2 and TF [46,[48][49][50][51]. Although it is generally known that the TF-FVIIa complex is present on the surface of hepatic Table 1. ...
... The primary function of melanocytes is the synthesis of melanin pigment. In skin each melanocytes is surrounded by approximately 36 keratinocytes 5,6 , to which they transfer their synthesized melanin 6,7 . ...
... Retinol stimulates fibroblasts to synthesize collagen fibres (stimulates the activity of fibroblasts and increases their number), improves skin elasticity (removes degenerated elastin fibers) and promotes angiogenesis [13]. Some studies indicate that retinol also enhances production of elastin fibres [14]. Moreover, retinol inhibits matrix metalloproteinases (MMPs) and enhances synthesis of tissue inhibitors of metalloproteinases (TIMPs) [15]. ...
