Authors
Ding, Z., Ma, G., Wang, F., Cheng, S., Li, P., Chen, Y., Chen, L., Ouyang, M., Wu, A., Pan, H., Cao, H.
Abstract
Skin wound healing is a complex, multicellular process essential for maintaining tissue integrity and homeostasis. Despite advances in biomaterial and cell-based therapies, the mechanisms by which adipose tissue regulates skin regeneration remain incompletely understood. Here, we identify adipocyte Kindlin-2 as a critical regulator of cutaneous wound repair. Adipocyte-specific deletion of Kindlin-2 markedly accelerates wound closure in mice by enhancing fibroblast proliferation, angiogenesis, and suppressing inflammation. Transplantation of visceral white adipose tissue (vWAT) from Kindlin-2-deficient mice similarly promotes wound healing, indicating an endocrine contribution of vWAT to skin regeneration. Mechanistically, loss of Kindlin-2 promotes E-cadherin proteolysis, resulting in increased release of a 33-kDa C-terminal fragment (CTF2) that activates {beta}-catenin signaling and induces transcriptional upregulation and secretion of insulin-like growth factor binding protein 2 (IGFBP2). Elevated circulating IGFBP2, in turn, stimulates integrin signaling in target cells to enhance wound repair. Pharmacological inhibition of {beta}-catenin signaling abrogated the healing advantage conferred by Kindlin-2 deficiency. Conversely, local delivery of IGFBP2 via lentiviral significantly accelerates wound closure in both wild-type C57BL/6 and diabetic ob/ob mice. Collectively, these findings uncover a previously unrecognized adipose-skin endocrine axis governed by Kindlin-2 and IGFBP2 that orchestrates tissue regeneration. Targeting this Kindlin-2/E-cadherin/{beta}-catenin/IGFBP2 pathway offers a promising therapeutic strategy for enhancing wound healing, particularly in chronic and diabetic wounds.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 04 Nov 2026.
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