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CTRP9 Regulates Growth, Differentiation, and Apoptosis in Human Keratinocytes through TGF?1-p38-Dependent Pathway.


ABSTRACT: Impairment of wound healing is a common problem in individuals with diabetes. Adiponectin, an adipocyte-derived cytokine, has many beneficial effects on metabolic disorders such as diabetes, obesity, hypertension, and dyslipidemia. C1q/TNF-Related Protein 9 (CTRP9), the closest paralog of adiponectin, has been reported to have beneficial effects on wound healing. In the current study, we demonstrate that CTRP9 regulates growth, differentiation, and apoptosis of HaCaT human keratinocytes. We found that CTRP9 augmented expression of transforming growth factor beta 1 (TGF?1) by transcription factor activator protein 1 (AP-1) binding activity and phosphorylation of p38 in a dose-dependent manner. Furthermore, siRNA-mediated suppression of TGF?1 reversed the increase in p38 phosphorylation induced by CTRP9. siRNA-mediated suppression of TGF?1 or p38 significantly abrogated the effects of CTRP9 on cell proliferation and differentiation while inducing apoptosis, implying that CTRP9 stimulates wound recovery through a TGF?1-dependent pathway in keratinocytes. Furthermore, intravenous injection of CTRP9 via tail vein suppressed mRNA expression of Ki67 and involucrin whereas it augmented TGF?1 mRNA expression and caspase 3 activity in skin of type 1 diabetes animal models. In conclusion, our results suggest that CTRP9 has suppressive effects on hyperkeratosis, providing a potentially effective therapeutic strategy for diabetic wounds.

SUBMITTER: Jung TW 

PROVIDER: S-EPMC5750709 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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CTRP9 Regulates Growth, Differentiation, and Apoptosis in Human Keratinocytes through TGFβ1-p38-Dependent Pathway.

Jung Tae Woo TW   Park Hyung Sub HS   Choi Geum Hee GH   Kim Daehwan D   Lee Taeseung T  

Molecules and cells 20171116 12


Impairment of wound healing is a common problem in individuals with diabetes. Adiponectin, an adipocyte-derived cytokine, has many beneficial effects on metabolic disorders such as diabetes, obesity, hypertension, and dyslipidemia. C1q/TNF-Related Protein 9 (CTRP9), the closest paralog of adiponectin, has been reported to have beneficial effects on wound healing. In the current study, we demonstrate that CTRP9 regulates growth, differentiation, and apoptosis of HaCaT human keratinocytes. We foun  ...[more]

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