Work

Activation/inactivation of Tregs mediated by Kv1.3 potassium channels synergistically with exosome secretion to regulate myocardial fibrosis

Year: 2025

Type: article

Abstract: Transforming growth factor-β (TGF-β) can promote myocardial fibrosis (MF). However, it was reported that regulatory T cells (Tregs) can reverse MF via secretion of anti-inflammatory cytokine IL-10. At present, the pathway of pro-myocardial fibrosis factors secreted by Tregs cells is not clear. Kv1.3 channel is closely related to the activation of Treg cells, which is a potential target for immuno-regulation. Here, we investigated whether the communication between co-cultured cells of Tregs and cardiac fibroblasts (CFs) was affected by the reduction of TGF-β secreted from Tregs by Kv1.3 knockdown, as well as whether exosome pathway mediates the pro-myocardial fibrosis process of Tregs. After co-culturing of Tregs transfected by RNA interference Kv1.3 potassium channel with CFs, we measured CFs proliferation, Tregs-derived exosomes level, TGF-β levels and expression of fibrosis-associated factors. In addition, after co-culturing of exosome extracted from Tregs with CFs, we also measured the CFs proliferation and TGF-β levels. Co-culture of CFs with Tregs-exosomes elevated TGF-β level, and promoted CFs proliferation. Importantly, Tregs transfected by RNA interference Kv1.3 channel reduced the accumulation of TGF-β, inhibited CFs proliferation and exocome releasing. The proliferation of CFs was activated with the co-cultured Tregs-exosome by secretion of TGF-β, which could be inhibited by blocking the Kv1.3 channel. Tregs could promote the viability of CFs by increasing the level of TGF-β primarily in the co-culture system, which was mediated by exosomes secreted from Tregs; and the promotion procedure could be inhibited by knocking-down of Kv1.3 potassium channels directly.

Source: Scientific Reports

DOI: 10.1038/s41598-025-28501-9

Authors: Mengjia Li, Yang Wu, Yongzheng Zhang, Zihang Wang, Lufeng Cheng, Xiang Xie

Institutions: Xinjiang Medical University, First Affiliated Hospital of Xinjiang Medical University

Language: English

Topic: Cardiac Fibrosis and Remodeling

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,690