| First Author | Gupta R | Year | 2025 |
| Journal | Wound Repair Regen | Volume | 33 |
| Issue | 6 | Pages | e70103 |
| PubMed ID | 41157851 | Mgi Jnum | J:375207 |
| Mgi Id | MGI:8264680 | Doi | 10.1111/wrr.70103 |
| Citation | Gupta R, et al. (2025) Endothelial betaII Spectrin Deletion Exacerbates Inflammation and Impairs Tissue Regeneration in Ischemic-Diabetic Skin Wound Healing. Wound Repair Regen 33(6):e70103 |
| abstractText | Impaired lower extremity wound healing due to diabetes presents a significant societal burden, as 25% of diabetic wounds lead to major amputations. While TGF-beta has been extensively studied in diabetic wound healing, the role of betaII spectrin (SPTBN1), a known adapter of SMAD3 in the canonical TGF-beta signalling pathway, remains unexplored. Single-cell RNA sequencing analysis revealed an increase in SPTBN1 expression in endothelial cells from non-diabetic skin to diabetic skin and ulcers. We found that silencing SPTBN1 in human umbilical vein endothelial cells (HUVECs) suppressed endothelial sprouting and tube formation. Based on these findings, we hypothesised that SPTBN1 regulates diabetic wound healing by modulating angiogenesis. To test this, we created Sptbn1 endothelial-specific conditional knockout (Sptbn1(ECKO)) mice and used the well-established streptozocin-induced diabetic excisional dorsal wound model. Interestingly, while Sptbn1(ECKO) mice showed delayed wound healing, the delay was not due to impaired angiogenesis, but rather due to excessive inflammation. Inflammation persisted in Sptbn1(ECKO) mice when it resolved in controls, as evidenced by higher numbers of neutrophils, inflammatory monocytes and greater iNOS staining intensity in the wound beds. Additionally, Sptbn1(ECKO) wounds had significantly less granulation tissue and fewer fibroblasts in the regenerative phase. Collectively, these findings suggest that betaII spectrin in endothelial cells is a potential therapeutic target in chronic diabetic wound healing. |
