Fermitin family homolog 2 (Kindlin-2) affects vascularization during the wound healing process by regulating the Wnt/β-catenin signaling pathway in vascular endothelial cells

Kindlin-2 is a member of the FERM-containing cytoskeletal protein family that regulates cell-matrix interactions. Previous studies have shown that Kindlin-2 recruits focal adhesion proteins and regulates integration by binding to the focal adhesion region of the integrin beta-segment. Although Kindlin-2 has been reported to be involved in various skin diseases and many kinds of tumors, its role in the skin wound healing process remains unclear. The aim of the present study was to investigate the role of Kindlin-2 in the regulation of wound healing. The effects of Kindlin-2 on wound healing were studied by a wound healing model, kindlin-2 (+/-) mice. The effects of Kindlin-2 on cell migration, cellular tube formation, and cell adhesion and spreading were evaluated in human umbilical vein endothelial cells (HUVECs) with downregulated Kindlin-2 expression. We found that the expression of kindlin-2 was elevated in wound healing tissues and that interfering with the expression of Kindlin-2 delayed the wound healing process and reduced neovascularization. We found that the wound healing of kindlin-2 (+/-) mice was delayed, with a decreased number of new blood vessels. Furthermore, depletion of Kindlin-2 impaired HUVEC spreading, migration and tube formation. Intriguingly, we found that kindlin-2 binds to beta-catenin in the Wnt/beta-catenin signaling pathway and cooperates with beta-catenin to enter the nucleus from the cytoplasm, activating the downstream Wnt/beta-catenin signaling pathway. Taken together, these results help to elucidate the mechanism of Kindlin-2 in the regulation of the wound healing process and provide a theoretical basis for further study of wound healing and abnormal healing.

Automated summary

Kindlin-2 is a key regulator in the wound healing process, affecting cell migration, tube formation, and adhesion, as well as interacting with the Wnt/beta-catenin signaling pathway. Interfering with Kindlin-2 expression delays wound healing and reduces neovascularization, highlighting its importance in tissue repair and suggesting potential therapeutic targets for abnormal wound healing.