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KMID : 0620920230550081770
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Experimental & Molecular Medicine
2023 Volume.55 No. 8 p.1770 ~ p.1782
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Inhibiting the cytosolic function of CXXC5 accelerates diabetic wound healing by enhancing angiogenesis and skin repair
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Kim Eun-Hwan
Seo Seol-Hwa
Hwang Yu-Mi
Ryu Yeong-Chan
Kim Hee-Jene
Lee Kyoung-Mi
Lee Jin-Woo
Park Kwang-Hwan
Choi Kang-Yell
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Abstract
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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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KEYWORD
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Diabetes complications, Regenerative medicine
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