Details

Autor(en) / Beteiligte

• Li, Anmao
• Gu, Lei
• Mu, Junhao
• Li, Yishi
• Wang, Xiaohui
• Jiang, Jinyue
• Bai, Yang
• Yang, Mingjin
• He, Chunyan
• Xiao, Rui
• Liao, Jiaxin
• Jin, Xingxing
• Xiao, Meiling
• Xiao, Yang
• Zhang, Xia
• Tan, Tairong
• Peng, Mingyu
• Xu, Li
• Guo, Shuliang

Titel

GATA6 triggers fibroblast activation and tracheal fibrosis through the Wnt/β-catenin pathway

Ist Teil von

• Cellular signalling, 2023-05, Vol.105, p.110593-110593, Article 110593

Ort / Verlag

England: Elsevier Inc

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• Tracheal fibrosis is a key abnormal repair process leading to fatal stenosis, characterized by excessive fibroblast activation and extracellular matrix (ECM) deposition. GATA6, a zinc finger-containing transcription factor, is involved in fibroblast activation, while its role in tracheal fibrosis remains obscure. The present study investigated the potential role of GATA6 as a novel regulator of tracheal fibrosis. It was found that GATA6 and α-smooth muscle actin (α-SMA) were obviously increased in tracheal fibrotic granulations and in TGFβ1-treated primary tracheal fibroblasts. GATA6 silencing inhibited TGFβ1-stimulated fibroblast proliferation and ECM synthesis, promoted cell apoptosis, and inactivated Wnt/β-catenin pathway, whereas GATA6 overexpression showed the reverse effects. SKL2001, an agonist of Wnt/β-catenin signaling, restored collagen1a1 and α-SMA expression which was suppressed by GATA6 silencing. Furthermore, in vivo, knockdown of GATA6 ameliorated tracheal fibrosis, as manifested by reduced tracheal stenosis and ECM deposition. GATA6 inhibition in rat tracheas also impaired granulation proliferation, increased apoptosis, and inactivated Wnt/β-catenin pathway. In conclusion, our findings indicate that GATA6 triggers fibroblast activation, cell proliferation, and apoptosis resistance in tracheal fibrosis via the Wnt/β-catenin signaling pathway. Targeting GATA6 may represent a promising therapeutic approach for tracheal fibrosis. [Display omitted] •GATA6 triggers tracheal fibrosis.•GATA6 promotes tracheal fibroblast activation via Wnt/β-catenin pathway.•GATA6 silencing alleviates tracheal fibrosis in rats.