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

  • Jung, Tae Woo (Research Administration Team, Seoul National University Bundang Hospital) ;
  • Park, Hyung Sub (Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Choi, Geum Hee (Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Kim, Daehwan (Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Lee, Taeseung (Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine)
  • Received : 2017.06.15
  • Accepted : 2017.11.05
  • Published : 2017.12.31


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 ($TGF{\beta}1$) by transcription factor activator protein 1 (AP-1) binding activity and phosphorylation of p38 in a dose-dependent manner. Furthermore, siRNA-mediated suppression of $TGF{\beta}1$ reversed the increase in p38 phosphorylation induced by CTRP9. siRNA-mediated suppression of $TGF{\beta}1$ or p38 significantly abrogated the effects of CTRP9 on cell proliferation and differentiation while inducing apoptosis, implying that CTRP9 stimulates wound recovery through a $TGF{\beta}1$-dependent pathway in keratinocytes. Furthermore, intravenous injection of CTRP9 via tail vein suppressed mRNA expression of Ki67 and involucrin whereas it augmented $TGF{\beta}1$ 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.


Supported by : National Research Foundation of Korea (NRF)


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