What question did this study set out to answer?

This research investigates the role of Gα12 in TGF-β-induced collagen production by lung fibroblasts, aiming to understand its implications in idiopathic pulmonary fibrosis.

May 20, 2026

C71-15 gα12 Is Involved in Tgf-β-Induced Extracellular Matrix Production by Human Lung Fibroblasts

Puntos clave

This research investigates the role of Gα12 in TGF-β-induced collagen production by lung fibroblasts, aiming to understand its implications in idiopathic pulmonary fibrosis.
Primary human lung fibroblasts were stimulated with TGF-β and assessed for collagen 1A1 and PAI expression.
Gene knockdown of Gα12 and Gαs was performed using siRNA, with experiments including n ≥ 3 unique cell lines.
The impact of Gαs agonist treprostinil on collagen production was evaluated before and after Gαs knockdown.
TGF-β significantly induced collagen 1A1 (p = 0.03) and PAI (p = 0.02) expression in lung fibroblasts.
Gα12 knockdown reduced TGF-β-induced collagen 1A1 expression (n = 3, p = 0.05), while PAI remained unaffected.
Treprostinil significantly inhibited collagen 1A1 production (n = 6, p = 0.04), indicating Gαs mediates this effect.

Resumen

Abstract Rationale Abnormal tissue repair and excessive extracellular matrix (ECM) deposition driven by the transition of fibroblasts into myofibroblasts characterizes idiopathic pulmonary fibrosis (IPF), a progressive fibrosing interstitial pneumonia. IPF carries a poor prognosis due to limited therapeutic options. Several G-protein coupled receptors (GPCRs) are impugned in the pathogenesis of IPF. In this study, we posit an interplay between G-protein families and TGF-β, a key regulator of ECM remodeling and fibrosis in human lung fibroblasts (HLF). Methods As a model of lung fibrosis, primary HLF were stimulated with TGF-β; collagen 1A1 and plasminogen activator inhibitor-1 (PAI) expression were then measured in the presence and absence of soluble receptor inhibitors (Gαq inhibitors) and decreased receptor expression with siRNA (Gα12 and Gαs siRNA). All experiments were performed in n ≥ 3 unique cell lines. Results TGF-β significantly induced collagen 1A1 (p = 0.03) and PAI (p = 0.02) in HLF. TGF-β induced collagen 1A1 (n = 9; p = 0.03) and PAI (n = 6; p = 0.03) was unaffected by Gαs knockdown. Treatment with the Gαs agonist (treprostinil) significantly inhibited TGF-β-induced collagen 1A1 (n = 6, p = 0.04). The treprostinil inhibitory effects was partially reversed following Gαs knockdown (n = 6, p = 0.05), suggesting that Gαs mediates treprostinil’s suppression of collagen 1A1. In contrast, Gαs was not required for treprostinil-mediated inhibition of PAI (n = 6, p = 0.03). The efficiency of Gαs knockdown exceeded 90%. A dose-response of the soluble Gαq inhibitor (100nM to 1µM) failed to alter TGF-β-induced collagen 1A1 or PAI expression (n = 4). In contrast, TGF-β-induced collagen 1A1 expression was reduced by Gα12 knockdown (n = 3, p = 0.05) while PAI remained unaffected. These findings suggest that Gα12 specifically mediates TGF-β-induced collagen 1A1 expression but not PAI. Conclusions Gα12 functions as a profibrotic G protein involved in TGF-β-induced collagen 1A1 expression. Elucidating the interplay between GPCR signaling, particularly the Gα12 subunit, and TGF-β may identify novel therapeutic strategies for IPF. This abstract is funded by: None

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Cite This Study

McNamara et al. (Fri,) studied this question.

synapsesocial.com/papers/6a0d5100f03e14405aa9d38d https://doi.org/https://doi.org/10.1093/ajrccm/aamag162.2783

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