ORIGINAL RESEARCH article

Front. Physiol.

Sec. Cell Physiology

Volume 16 - 2025 | doi: 10.3389/fphys.2025.1577118

TRPC3 Inhibition Induces Myofibroblast Differentiation in Diabetic Dermal Fibroblasts

Provisionally accepted
  • University of Tennessee Health Science Center (UTHSC), Memphis, United States

The final, formatted version of the article will be published soon.

Diabetic wounds present a significant healthcare challenge due to impaired healing mechanisms, with dermal fibroblasts playing a crucial role in tissue repair. This study investigates the role of transient receptor potential canonical-3 (TRPC3) in the dysfunction of diabetic fibroblasts and explores the therapeutic potential of TRPC3 inhibition. Findings reveal that TRPC3 expression is significantly elevated in diabetic dermal fibroblasts, which correlates with suppressed transforming growth factorbeta (TGF-β) signaling and impaired differentiation into myofibroblasts. Inhibiting TRPC3 effectively restores fibroblast functionality by upregulating TGF-β1 and its downstream effector, SMAD4. This restoration enhances the expression of key myofibroblast markers, such as α-smooth muscle actin (ACTA2) and type I collagen (COL1a1), which are essential for wound contraction and extracellular matrix remodeling. These results establish TRPC3 as a critical regulator of fibroblast activity and present TRPC3 inhibition as a promising therapeutic strategy for improving wound healing in diabetic patients.

Keywords: diabetic dermal fibroblast, myofibroblast, TRPC3, Pharmacological inhibition, TGF-β signaling

Received: 15 Feb 2025; Accepted: 21 Apr 2025.

Copyright: © 2025 Toogood, Evans, Zhang, Patel, Meng, BODA, Li and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Junwang Xu, University of Tennessee Health Science Center (UTHSC), Memphis, United States

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