2. Academic Validation
  3. Inhibiting the cytosolic function of CXXC5 accelerates diabetic wound healing by enhancing angiogenesis and skin repair

Inhibiting the cytosolic function of CXXC5 accelerates diabetic wound healing by enhancing angiogenesis and skin repair

  • Exp Mol Med. 2023 Aug;55(8):1770-1782. doi: 10.1038/s12276-023-01064-3.
Eunhwan Kim 1,  Seol Hwa Seo 1,  Yumi Hwang 1,  Yeong Chan Ryu 1,  Heejene Kim 1,  Kyoung-Mi Lee 2,  Jin Woo Lee 2 3,  Kwang Hwan Park 4,  Kang-Yell Choi 5 6
Affiliations

Affiliations

  • 1 Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea.
  • 2 Department of Orthopedic Surgery, Yonsei University College of Medicine, Seoul, 03722, South Korea.
  • 3 Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, 03722, South Korea.
  • 4 Department of Orthopedic Surgery, Yonsei University College of Medicine, Seoul, 03722, South Korea. khpark@yuhs.ac.
  • 5 Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea. kychoi@yonsei.ac.kr.
  • 6 CK Regeon Inc, Engineering Research Park, 50 Yonsei Ro, Seodaemun-Gu, Seoul, 03722, South Korea. kychoi@yonsei.ac.kr.
PMID: 37524876 DOI: 10.1038/s12276-023-01064-3
Abstract

Diabetic wound healing, including diabetic foot ulcer (DFU), is a serious complication of diabetes. Considering the complexity of DFU development, the identification of a factor that mediates multiple pathogeneses is important for treatment. In this study, we found that CXXC-type Zinc Finger Protein 5 (CXXC5), a negative regulator of the Wnt/β-catenin pathway, was overexpressed with suppression of the Wnt/β-catenin pathway and its target genes involved in wound healing and angiogenesis in the wound tissues of DFU patients and diabetes-induced model mice. KY19334, a small molecule that activates the Wnt/β-catenin pathway by inhibiting the CXXC5-Dvl interaction, accelerated wound healing in diabetic mice. The enhancement of diabetic wound healing could be achieved by restoring the suppressed Wnt/β-catenin signaling and subsequently inducing its target genes. Moreover, KY19334 induced angiogenesis in hindlimb ischemia model mice. Overall, these findings revealed that restorative activation of Wnt/β-catenin signaling by inhibiting the function of cytosolic CXXC5 could be a therapeutic approach for treating DFUs.

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