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Therapeutic strategies to target connective tissue growth factor in fibrotic lung diseases
Takuma Isshiki1, Safaa Naiel2, Megan Vierhout2
1Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, 5o Charlton Avenue East, Hamilton, ON, L8N 4A6, Canada; Department of Pathology and Molecular Medicine, McMaster Immunology Research Center, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 48L, Canada; Department of Respiratory Medicine, Toho University School of Medicine, 6-11-1 Omori Nisi, Ota-ku, Tokyo 143-8541, Japan.
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.
Insights
Connective tissue growth factor (CTGF) drives lung fibrosis by promoting fibroblast activation and epithelial changes. Inhibiting CTGF signaling shows promise for treating idiopathic pulmonary fibrosis (IPF) and other fibrotic lung diseases.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Biochemistry
Background:
- Interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF), lack effective treatments.
- Connective tissue growth factor (CTGF), also known as CCN2, is implicated in fibrotic processes.
Approach:
- This review systematically analyzes the pathogenic role of CTGF in pulmonary fibrosis.
- It discusses current therapeutic strategies targeting the CTGF signaling pathway.
Key Points:
- CTGF promotes lung fibrosis via fibroblast-to-myofibroblast transdifferentiation and epithelial-mesenchymal transition (EMT).
- CTGF signaling cooperates with other fibrotic mediators like TGF-β.
- Inhibition of CTGF has demonstrated efficacy in preclinical models of lung fibrosis.
Conclusions:
- The CTGF signaling pathway represents a promising therapeutic target for IPF and other fibrotic lung conditions.
- Further research into CTGF-targeted therapies is warranted for effective treatment of pulmonary fibrosis.
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