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.