RIP4 is a target of multiple signal transduction pathways in keratinocytes: implications for epidermal differentiation and cutaneous wound repair.
Receptor interacting protein 4 (RIP4) is an important regulator of epidermal morphogenesis during embryonic development. We could previously show that expression of the rip4 gene is strongly downregulated in cutaneous wound repair, which might be initiated by a broad variety of growth factors and cytokines. Here, we demonstrate that in keratinocytes, rip4 expression is controlled by a multitude of different signal transduction pathways, such as the p38 mitogen-activated protein kinase (MAPK) and the nuclear factor kappa B (NF-kappaB) cascade, in a unique and specific manner. Furthermore, we show that the steroid dexamethasone abolishes the physiological rip4 downregulation after injury and might thus contribute to the phenotype of reduced and delayed wound reepithelialization seen in glucocorticoid-treated patients. As a whole, our data indicate that rip4 expression is regulated in a complex manner, which might have therapeutic implications.
Adams
Stephanie
S
Charité, University Medicine Berlin, Institute of Physiology, Arnimallee 22, D-14195 Berlin, Germany.
Munz
Barbara
B
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D016895:Culture Media, Serum-Free; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D003907:Dexamethasone; D006861:Hydrogen Peroxide; D011494:Protein Kinases; C417187:RIPK4 protein, human; D017346:Protein Serine-Threonine Kinases; C430884:Ripk4 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases; D003474:Curcumin; D002118:Calcium