Deciphering the cellular mechanisms underlying fibrosis-associated diseases and therapeutic avenues

Abstract

Fibrosis is the excessive deposition of extracellular matrix components, which results in disruption of tissue architecture and loss of organ function. Fibrosis leads to high morbidity and mortality worldwide, mainly due to the lack of effective therapeutic strategies against fibrosis. It is generally accepted that fibrosis occurs during an aberrant wound healing process and shares a common pathogenesis across different organs such as the heart, liver, kidney, and lung. A better understanding of the fibrosis-related cellular and molecular mechanisms will be helpful for development of targeted drug therapies. Extensive studies revealed that numerous mediators contributed to fibrogenesis, suggesting that targeting these mediators may be an effective therapeutic strategy for antifibrosis. In this review, we describe a number of mediators involved in tissue fibrosis, including aryl hydrocarbon receptor, Yes-associated protein, cannabinoid receptors, angiopoietin-like protein 2, high mobility group box 1, angiotensin-converting enzyme 2, sphingosine 1-phosphate receptor-1, SH2 domain-containing phosphatase-2, and long non-coding RNAs, with the goal that drugs targeting these important mediators might exhibit a beneficial effect on antifibrosis. In addition, these mediators show profibrotic effects on multiple tissues, suggesting that targeting these mediators will exert antifibrotic effects on different organs. Furthermore, we present a variety of compounds that exhibit therapeutic effects against fibrosis. This review suggests therapeutic avenues for targeting organ fibrosis and concurrently identifies challenges and opportunities for designing new therapeutic strategies against fibrosis.

Keywords: Aryl hydrocarbon receptor; Epithelial-mesenchymal transition; Long non-coding RNAs; Macrophage-myofibroblast transition; Macrophages; PubChem CID 10228; PubChem CID 14296; PubChem CID 15352; PubChem CID 15625; PubChem CID 164676; PubChem CID 5282150; PubChem CID 5471851; PubChem CID 6438568; PubChem CID 6441416; PubChem CID 969516; Tissue fibrosis.