Journal of cellular physiologyJan 20, 2022

Blocking RUNX1 stops lung support cells from becoming scar-forming cells

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 6, 2026

Abstract

RUNX1 expression was significantly increased in the lungs of bleomycin-injected mice compared to saline-treated mice.

Idiopathic pulmonary fibrosis (IPF) is associated with excessive accumulation of extracellular matrix proteins that lead to stiff lung tissue.
Transforming growth factor β (TGF-β) stimulation resulted in significantly higher RUNX1 expression in human lung fibroblasts at both mRNA and protein levels.
Inhibition of RUNX1 in human lung fibroblasts reduced their differentiation into myofibroblasts, as indicated by decreased levels of alpha-smooth muscle actin, TGF-β, fibronectin 1, and collagen 1A1.
RUNX1 expression in TGF-β-stimulated lung fibroblasts is facilitated by increased mRNA stability through interaction with the RNA-binding protein human antigen R.
Higher RUNX1 levels may promote the differentiation of fibroblasts into myofibroblasts, contributing to lung fibrosis.

Simplified

Pathological fibrosis contributes to progression of various diseases, for which the therapeutic options are limited. Idiopathic pulmonary fibrosis (IPF) is one such progressive and fatal interstitial fibrotic disease that is often characterized by excessive accumulation of extracellular matrix (ECM) proteins leading to stiff lung tissue and impaired gas exchange. However, the molecular mechanisms underlying IPF progression remain largely unknown. In this study, we determined the role of Runt-related transcription factor 1 (RUNX1), an evolutionarily conserved transcription factor, in the differentiation of human lung fibroblasts (HLFs) in vitro and in an animal model of bleomycin (BLM)-induced lung fibrosis. We observed that the expression of RUNX1 was significantly increased in the lungs of BLM-injected mice as compared to saline-treated mice. Furthermore, HLFs stimulated with transforming growth factor β (TGF-β) showed significantly higher RUNX1 expression at both mRNA and protein levels, and compartmentalization in the nucleus. Inhibition of RUNX1 in HLFs (using siRNA) showed a significant reduction in the differentiation of fibroblasts into myofibroblasts as evidenced by reduced expression of alpha-smooth muscle actin (α-SMA), TGF-β and ECM proteins such as fibronectin 1 (FN1), and collagen 1A1 (COL1A1). Mechanistic studies revealed that the increased expression of RUNX1 in TGF-β-stimulated lung fibroblasts is due to enhanced mRNA stability of RUNX1 through selective interaction with the RNA-binding profibrotic protein, human antigen R (HuR). Collectively, our data demonstrate that increased expression of RUNX1 augments processes involved in lung fibrosis including the differentiation of fibroblasts into collagen-synthesizing myofibroblasts. Our study suggests that targeting RUNX1 could limit the progression of organ fibrosis in diseases characterized by abnormal collagen deposition.

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Blocking RUNX1 stops lung support cells from becoming scar-forming cells

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