Transient synthesis of K6 and K16 keratins in regenerating rabbit corneal epithelium: keratin markers for an alternative pathway of keratinocyte differentiation

Schermer, Alexander; Jester, James V.; Hardy, Carolyn; Milano, Danielle; Sun, Tung‐Tien

doi:10.1111/j.1432-0436.1989.tb00611.x

Cited by 115 publications

(85 citation statements)

References 45 publications

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“…82 In stratified epithelia, it has been suggested that K6 and K16 are up-regulated during chronic hyperproliferation, such as in psoriatic skin, or abnormal differentiation, such as a cancer, and that the ubiquitous expression of K6 and K16 is correlated with changes in keratinocyte differentiation. 77,[83][84][85][86] In agreement with these documents, overexpression of the human K16 gene in transgenic mice has been reported to initiate re-organization of the intermediate filament network in keratinocytes in both outer root sheath and epidermis, resulting in aberrant keratinization and hyperproliferation as well as the rescue of the lethal skin blistering phenotype of K14-null mice. 87,88 These observations indicate that K6 and it partners K16 and/or K17 play a direct role in eliciting the cutaneous morphological changes to regulate epidermal proliferation and differentiation.…”

Section: Discussionsupporting

confidence: 56%

Mechanistic Effects of Long-Term Ultraviolet B Irradiation Induce Epidermal and Dermal Changes in Human Skin Xenografts

Hachiya

Sriwiriyanont

Fujimura

et al. 2009

The American Journal of Pathology

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UVB irradiation has been reported to induce photoaging and suppress systemic immune function that could lead to photocarcinogenesis. However, because of the paucity of an UVB-induced photodamaged skin model, precise and temporal mechanism(s) underlying the deleterious effects of long-term UVB exposure on human skin have yet to be delineated. In this study, we established a model using human skin xenografted onto severe combined immunodeficient mice, which were subsequently challenged by repeated UVB irradiation for 6 weeks. Three-dimensional optical image analysis of skin replicas and noninvasive biophysical measurements illustrated a significant increase in skin surface roughness, similar to premature photoaging, and a significant loss of skin elasticity after long-term UVB exposure. Resembling authentically aged skin, UVB-exposed samples exhibited significant increases in epithelial keratins (K6, K16, K17), elastins, and matrix metalloproteinases (MMP-1, MMP-9, MMP-12) as well as degradation of collagens (I, IV, VII). The UVB-induced deterioration of fibrous keratin intermediate filaments was also observed in the stratum corneum. Additionally, similarities in gene expression patterns between our model and chronologically aged skin substantiated the plausible relationship between photodamage and chronological age. Furthermore , severe skin photodamage was observed when neutralizing antibodies against TIMP-1 , an endogenous inhibitor of MMPs , were administered during the UVB exposure regimen. Taken together , these findings suggest that our skin xenograft model recapitulates premature photoaged skin and provides a comprehensive tool with which to assess the deleterious effects of UVB irradiation.

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Section: Discussionsupporting

confidence: 56%

Mechanistic Effects of Long-Term Ultraviolet B Irradiation Induce Epidermal and Dermal Changes in Human Skin Xenografts

Hachiya

Sriwiriyanont

Fujimura

et al. 2009

The American Journal of Pathology

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“…Cytokeratins are polypeptides that constitute the most abundant type of intermediate filaments in epithelial cells. 38,39 Thus, the expression of several cytokeratins in both PBMCs and circulating precursor cells in treatment with our established culture medium allowed us in this study to confirm their epithelial determination. In support of this, we also showed that involucrin, which is a component of mature epithelial cells, 40,41 is also expressed by epithelial-like cells in our culture condition used.…”

Section: Discussionmentioning

confidence: 78%

Transdifferentiation of Peripheral Blood Mononuclear Cells into Epithelial-Like Cells

Medina

Kilani

Carr

et al. 2007

The American Journal of Pathology

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Bone marrow-derived stem cells have the potential to transdifferentiate into unexpected peripheral cells. We hypothesize that circulating bone marrow-derived stem cells might have the capacity to transdifferentiate into epithelial-like cells and release matrix metalloproteinase-1-modulating factors such as 14-3-3 for dermal fibroblasts. We have characterized a subset of peripheral blood mononuclear cells (PBMCs) that develops an epithelial-like profile. Our findings show that these cells develop epithelial-like morphology and express 14-3-3 and keratin-5, -8 as early as day 7 and day 21, respectively. When compared with control, conditioned media collected from PBMCs in advanced epithelial-like differentiation (cultures on days 28, 35, and 42) increased the matrix metalloproteinase-1 expression in dermal fibroblasts (P < 0.01). The depletion of 14-3-3 from these conditioned media by immunoprecipitation reduced the effect by 39.5% (P value, 0.05). Therefore, the releasable 14-3-3 from PBMC-derived epithelial-like cells is involved in this process. Our findings provide new insights into the PBMC transdifferentiation to generate epithelial-like cells and subsequently release of 14-3-3 that will disclose new therapeutic alternatives for different dermal clinical settings. (Am J Pathol

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“…Interestingly, TGF-/~s seem to elicit these changes in keratinizing epidermal cells at least in part independently of their action on basal cells. Collectively, these studies have led to the notion that the epidermal phenotype associated with wound healing and many hyperproliferative diseases may not relate to hyperproliferation, per se, but rather is a reflection of environmental changes, which, in some circumstances, may include active TGF-Bs (Mansbridge and Hanawalt, 1988;Kopan and Fuchs, 1989;Schermer et al, 1989;Choi and Fuchs, 1990).…”

Section: Negative Growth Regulatorsmentioning

confidence: 99%

Epidermal differentiation: the bare essentials.

Fuchs

1990

The Journal of Cell Biology

613

481

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N the past ten years, there have been a number of major scientific discoveries in the field of epidermal differentiation. We owe many of these findings to the development of model tissue culture systems, and to technological advances in molecular biology. In this article, I will review some important aspects of the biology of terminal differentiation in vivo and in vitro, and highlight the recent advances in elucidating the molecular mechanism underlying these processes.

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Transient synthesis of K6 and K16 keratins in regenerating rabbit corneal epithelium: keratin markers for an alternative pathway of keratinocyte differentiation

Cited by 115 publications

References 45 publications

Mechanistic Effects of Long-Term Ultraviolet B Irradiation Induce Epidermal and Dermal Changes in Human Skin Xenografts

Mechanistic Effects of Long-Term Ultraviolet B Irradiation Induce Epidermal and Dermal Changes in Human Skin Xenografts

Transdifferentiation of Peripheral Blood Mononuclear Cells into Epithelial-Like Cells

Epidermal differentiation: the bare essentials.

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