scholarly journals Transforming growth factor-beta 1 modulates beta 1 and beta 5 integrin receptors and induces the de novo expression of the alpha v beta 6 heterodimer in normal human keratinocytes: implications for wound healing.

1995 ◽  
Vol 129 (3) ◽  
pp. 853-865 ◽  
Author(s):  
G Zambruno ◽  
P C Marchisio ◽  
A Marconi ◽  
C Vaschieri ◽  
A Melchiori ◽  
...  
Keyword(s):  
Wound Healing ◽  
De Novo ◽  
Human Keratinocytes ◽  
General Mechanism ◽  
Integrin Expression ◽  
Tgf Beta ◽  
Fibronectin Receptor ◽  
Receptor Alpha ◽  
Normal Human Keratinocytes ◽  
Normal Human

The molecular mechanism underlying the promotion of wound healing by TGF-beta 1 is incompletely understood. We report that TGF-beta 1 regulates the regenerative/migratory phenotype of normal human keratinocytes by modulating their integrin receptor repertoire. In growing keratinocyte colonies but not in fully stratified cultured epidermis, TGF-beta 1: (a) strongly upregulates the expression of the fibronectin receptor alpha 5 beta 1, the vitronectin receptor alpha v beta 5, and the collagen receptor alpha 2 beta 1 by differentially modulating the synthesis of their alpha and beta subunits; (b) downregulates the multifunctional alpha 3 beta 1 heterodimer; (c) induces the de novo expression and surface exposure of the alpha v beta 6 fibronectin receptor; (d) stimulates keratinocyte migration toward fibronectin and vitronectin; (e) induces a marked perturbation of the general mechanism of polarized domain sorting of both beta 1 and beta 4 dimers; and (f) causes a pericellular redistribution of alpha v beta 5. These data suggest that alpha 5 beta 1, alpha v beta 6, and alpha v beta 5, not routinely used by keratinocytes resting on an intact basement membrane, act as "emergency" receptors, and uncover at least one of the molecular mechanisms responsible for the peculiar integrin expression in healing human wounds. Indeed, TGF-beta 1 reproduces the integrin expression pattern of keratinocytes located at the injury site, particularly of cells in the migrating epithelial tongue at the leading edge of the wound. Since these keratinocytes are inhibited in their proliferative capacity, these data might account for the apparent paradox of a TGF-beta 1-dependent stimulation of epidermal wound healing associated with a growth inhibitory effect on epithelial cells.

Electrospinning of collagen nanofibers: Effects on the behavior of normal human keratinocytes and early-stage wound healing

Biomaterials ◽  
2006 ◽  
Vol 27 (8) ◽  
pp. 1452-1461 ◽  
Author(s):  
Kyong Su Rho ◽  
Lim Jeong ◽  
Gene Lee ◽  
Byoung-Moo Seo ◽  
Yoon Jeong Park ◽  
...  
Keyword(s):  
Wound Healing ◽  
Early Stage ◽  
Human Keratinocytes ◽  
Normal Human Keratinocytes ◽  
Normal Human

scholarly journals Human Papillomavirus Type 8 E2 Protein Unravels JunB/Fra-1 as an Activator of the β4-Integrin Gene in Human Keratinocytes

2009 ◽  
Vol 84 (3) ◽  
pp. 1376-1386 ◽  
Author(s):  
Monika Oldak ◽  
Radoslaw B. Maksym ◽  
Tanya Sperling ◽  
Moshe Yaniv ◽  
Hans Smola ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Life Cycle ◽  
Human Keratinocytes ◽  
Binding Activity ◽  
Keratinocyte Differentiation ◽  
Integrin Expression ◽  
E2 Protein ◽  
Normal Human Keratinocytes ◽  
Normal Human ◽  
Β4 Integrin

ABSTRACT The papillomavirus life cycle parallels keratinocyte differentiation in stratifying epithelia. We have previously shown that the human papillomavirus type 8 (HPV8) E2 protein downregulates β4-integrin expression in normal human keratinocytes, which may trigger subsequent differentiation steps. Here, we demonstrate that the DNA binding domain of HPV8 E2 is sufficient to displace a cellular factor from the β4-integrin promoter. We identified the E2-displaceable factor as activator protein 1 (AP-1), a heteromeric transcription factor with differentiation-specific expression in the epithelium. β4-Integrin-positive epithelial cells displayed strong AP-1 binding activity. Both AP-1 binding activity and β4-integrin expression were coregulated during keratinocyte differentiation suggesting the involvement of AP-1 in β4-integrin expression. In normal human keratinocytes the AP-1 complex was composed of JunB and Fra-1 subunits. Chromatin immunoprecipitation assays confirmed that JunB/Fra-1 proteins interact in vivo with the β4-integrin promoter and that JunB/Fra-1 promoter occupancy is reduced during keratinocyte differentiation as well as in HPV8 E2 positive keratinocytes. Ectopic expression of the tethered JunB/Fra-1 heterodimer in normal human keratinocytes activated the β4-integrin promoter, while coexpression of HPV8 E2 reverted the JunB/Fra-1 effect. In summary, we identified a novel mechanism of human β4-integrin regulation that is specifically targeted by the HPV8 E2 protein mimicking transcriptional conditions of differentiation. This may explain the early steps of how HPV8 commits its host cells to the differentiation process required for the viral life cycle.

scholarly journals Hyaluronic Acid and Wound Healing

2015 ◽  
Vol 18 (1) ◽  
pp. 53 ◽  
Author(s):  
Manuela G Neuman ◽  
Radu M Nanau ◽  
Loida Oruña-Sanchez ◽  
Gabriel Coto
Keyword(s):  
Wound Healing ◽  
Hyaluronic Acid ◽  
Wound Repair ◽  
Original Work ◽  
Human Keratinocytes ◽  
Review Of The Literature ◽  
Skin Repair ◽  
Normal Human Keratinocytes ◽  
Normal Human

Background. We developed an experimental model of ethanol-induced dermatotoxicity and hepatocytoxicity using normal human keratinocytes and normal human hepatocytes that preserve inducible cytochrome p450 activities. The original work was described in several articles. The objective of this study was to determine whether hyaluronic acid attenuates skin necrosis, and to further clarify its uses in wound repair in humans, animal models and in vitro studies. Methods. We performed a systematic review of the literature using the terms “hyaluronic acid” and “wound healing”. PubMed was searched for studies published during the period 2010-2014. Results. Hyaluronic acid is used in tissue regeneration alone or in combination with herbal or Western medicine. Scaffolds made up of hyaluronic acid were used to embed basic fibroblast growth factor. Conclusion. Hyaluronic acid extracts are safe and efficacious products to be used in skin repair. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals UVB-mediated activation of p38 mitogen-activated protein kinase enhances resistance of normal human keratinocytes to apoptosis by stabilizing cytoplasmic p53

2002 ◽  
Vol 365 (1) ◽  
pp. 133-145 ◽  
Author(s):  
Nadine CHOUINARD ◽  
Kristoffer VALERIE ◽  
Mahmoud ROUABHIA ◽  
Jacques HUOT
Keyword(s):  
Adaptive Response ◽  
Human Keratinocytes ◽  
Dominant Negative ◽  
Mitogen Activated Protein Kinase ◽  
Dominant Negative Mutant ◽  
Normal Human Keratinocytes ◽  
Mitogen Activated Protein ◽  
Normal Human ◽  
Induced Apoptosis ◽  
Negative Mutant

Human keratinocytes respond to UV rays by developing a fast adaptive response that contributes to maintaining their functions and survival. We investigated the role of the mitogen-activated protein kinase pathways in transducing the UV signals in normal human keratinocytes. We found that UVA, UVB or UVC induced a marked and persistent activation of p38, whereas c-Jun N-terminal kinase or extracellular signal-regulated kinase were less or not activated respectively. Inhibition of p38 activity by expression of a dominant-negative mutant of p38 or with SB203580 impaired cell viability and led to an increase in UVB-induced apoptosis. This sensitization to apoptosis was independent of caspase activities. Inhibition of p38 did not sensitize transformed HaCaT keratinocytes to UVB-induced apoptosis. In normal keratinocytes, expression of a dominant-negative mutant of p53 increased UVB-induced cell death, pointing to a role for p53. In these cells, UVB triggered a p38-dependent phosphorylation of p53 on Ser-15. This phosphorylation was associated with an SB203580-sensitive accumulation of p53, even in the presence of a serine phosphatase inhibitor. Accumulated p53 was localized mainly in the cytoplasm, independently of CRM1 nuclear export. In HaCaT cells, p53 was localized exclusively in the nucleus and its distribution and level were not affected by UVB or p38 inhibition. However, UVB induced an SB203580-insensitive phosphorylation on Ser-15 of mutated p53. Overall, our results suggest that, in normal human keratinocytes, protection against UVB depends on p38-mediated phosphorylation and stabilization of p53 and is tightly associated with the cytoplasmic sequestration of wild-type p53. We conclude that the p38/p53 pathway plays a key role in the adaptive response of normal human keratinocytes against UV stress.

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