Therapeutic strategies to target connective tissue growth factor in fibrotic lung diseases

Pharmacol Ther. 2024 Jan:253:108578. doi: 10.1016/j.pharmthera.2023.108578. Epub 2023 Dec 15.

Abstract

The treatment of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF), remains challenging as current available antifibrotic agents are not effective in halting disease progression. Connective tissue growth factor (CTGF), also known as cellular communication factor 2 (CCN2), is a member of the CCN family of proteins that regulates cell signaling through cell surface receptors such as integrins, the activity of cytokines/growth factors, and the turnover of extracellular matrix (ECM) proteins. Accumulating evidence indicates that CTGF plays a crucial role in promoting lung fibrosis through multiple processes, including inducing transdifferentiation of fibroblasts to myofibroblasts, epithelial-mesenchymal transition (EMT), and cooperating with other fibrotic mediators such as TGF-β. Increased expression of CTGF has been observed in fibrotic lungs and inhibiting CTGF signaling has been shown to suppress lung fibrosis in several animal models. Thus, the CTGF signaling pathway is emerging as a potential therapeutic target in IPF and other pulmonary fibrotic conditions. This review provides a comprehensive overview of the current evidence on the pathogenic role of CTGF in pulmonary fibrosis and discusses the current therapeutic agents targeting CTGF using a systematic review approach.

Keywords: CTGF; IPF; Interstitial pneumonia; Pulmonary fibrosis; Therapeutics.

Publication types

  • Systematic Review
  • Review

MeSH terms

  • Animals
  • Connective Tissue Growth Factor* / metabolism
  • Fibroblasts / metabolism
  • Fibrosis
  • Idiopathic Pulmonary Fibrosis* / drug therapy
  • Idiopathic Pulmonary Fibrosis* / pathology
  • Lung / metabolism
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta1

Substances

  • Connective Tissue Growth Factor
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1