Notch signaling regulates pulmonary fibrosis

Front Cell Dev Biol. 2024 Oct 10:12:1450038. doi: 10.3389/fcell.2024.1450038. eCollection 2024.

Abstract

Pulmonary fibrosis is a progressive interstitial lung disease associated with aging. The pathogenesis of pulmonary fibrosis remains unclear, however, alveolar epithelial cell injury, myofibroblast activation, and extracellular matrix (ECM) accumulation are recognized as key contributors. Moreover, recent studies have implicated cellular senescence, endothelial-mesenchymal transition (EndMT), and epigenetic modifications in the pathogenesis of fibrotic diseases. Various signaling pathways regulate pulmonary fibrosis, including the TGF-β, Notch, Wnt, Hedgehog, and mTOR pathways. Among these, the TGF-β pathway is extensively studied, while the Notch pathway has emerged as a recent research focus. The Notch pathway influences the fibrotic process by modulating immune cell differentiation (e.g., macrophages, lymphocytes), inhibiting autophagy, and promoting interstitial transformation. Consequently, inhibiting Notch signaling represents a promising approach to mitigating pulmonary fibrosis. In this review, we discuss the role of Notch signaling pathway in pulmonary fibrosis, aiming to offer insights for future therapeutic investigations.

Keywords: autophagy; macrophage polarization; mesenchymal transformation; notch; pulmonary fibrosis.

Publication types

  • Review

Grants and funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.