Drugs targeting CTGF in the treatment of pulmonary fibrosis

Abstract

Pulmonary fibrosis represents the final alteration seen in a wide variety of lung disorders characterized by increased fibroblast activity and the accumulation of substantial amounts of extracellular matrix, along with inflammatory damage and the breakdown of tissue architecture. This condition is marked by a significant mortality rate and a lack of effective treatments. The depositing of an excessive quantity of extracellular matrix protein follows the damage to lung capillaries and alveolar epithelial cells, leading to pulmonary fibrosis and irreversible damage to lung function. It has been proposed that the connective tissue growth factor (CTGF) plays a critical role in the advancement of pulmonary fibrosis by enhancing the accumulation of the extracellular matrix and exacerbating fibrosis. In this context, the significance of CTGF in pulmonary fibrosis is examined, and a summary of the development of drugs targeting CTGF for the treatment of pulmonary fibrosis is provided.

Keywords: CTGF; drugs; pulmonary fibrosis; treatment.

FIGURE 1

Overview of molecular mechanism of pulmonary fibrosis. Some alveolar type II cells may undergo the EMT process and differentiate into fibroblasts and myofibroblasts. Original and differentiated myofibroblasts are activated by TGF‐β and secrete ECM, leading to increased pulmonary fibrosis.

FIGURE 2

Schematic summary of the mechanisms involved in CTGF in pulmonary fibrosis. CTGF is secreted from fibroblasts into the extracellular space and acts on fibroblasts. (1) CTGF/RAC1/MLK3/AP‐1 affects the components of ECM and aggravates pulmonary fibrosis; (2) Differentiation of lung fibroblasts is induced by CTGF/Pref‐1/α5β1/ERK/AP‐1; (3) TGF‐β induces CTGF expression through ERK/ADAM17/RSK1/ C/EBP‐β pathway; (4) CTGF promotes upregulation of MMP‐13 through αvβ3 /FAK/ERK/NF‐κB dependent pathway and aggravates pulmonary fibrosis.