Mol. Cells 2017; 40(12):   https://doi.org/10.14348/molcells.2017.0097
CTRP9 Regulates Growth, Differentiation, and Apoptosis in Human Keratinocytes through TGFβ1-p38-Dependent Pathway
Tae Woo Jung1,2, Hyung Sub Park2, Geum Hee Choi2, Daehwan Kim2, and Taeseung Lee2,3,* 
1Research Administration Team, Seoul National University Bundang Hospital, Seongnam 13620, Korea, 2Department of Surgery,
Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea, 3Department of Surgery, Seoul National University College of Medicine, Seoul 03080, Korea
*Correspondence: tslee@snubh.org
Received June 15, 2017; Revised November 1, 2017; Accepted November 5, 2017.; Published online November 16, 2017.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

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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 (TGFβ1) by transcription factor activator protein 1 (AP-1) binding activity and phosphorylation of p38 in a dosedependent manner. Furthermore, siRNA-mediated suppression of TGFβ1 reversed the increase in p38 phosphorylation induced by CTRP9. siRNA-mediated suppression of TGFβ1 or p38 significantly abrogated the effects of CTRP9 on cell proliferation and differentiation while inducing apoptosis, implying that CTRP9 stimulates wound recovery through a TGFβ1- dependent pathway in keratinocytes. Furthermore, intravenously injection of CTRP9 via tail vein suppressed mRNA expression of Ki67 and involucrin whereas it augmented TGFβ1 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.
Keywords: apoptosis, C1q/TNF-Related Protein 9, differentiation,
p38, proliferation, transforming growth factor beta 1


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