Small molecules against the origin and activation of myofibroblast for renal interstitial fibrosis therapy

Area of Science:

• Nephrology
• Pathology
• Pharmacology

Background:

• Renal interstitial fibrosis (RIF) is a critical pathological process in chronic kidney diseases, leading to significant morbidity and mortality worldwide.
• Myofibroblasts are the primary cellular effectors driving RIF, and their origin and activation are key to fibrogenesis.
• Current therapeutic options for RIF are limited, highlighting an urgent need for effective treatments.

Purpose of the Study:

• To review the mechanisms underlying the origin and activation of renal myofibroblasts in RIF.
• To explore the therapeutic potential of small molecules targeting these myofibroblast pathways for RIF treatment.

Main Methods:

• Literature review focusing on cellular origins of renal myofibroblasts.
• Analysis of signaling pathways (TGF-β1, mTOR, ROS) and epigenetic modifications (histone acetylation, ncRNA) involved in myofibroblast activation.
• Examination of studies on small molecules demonstrating therapeutic effects on RIF.

Main Results:

• Multiple cell types, including fibroblasts, epithelial cells, endothelial cells, macrophages, and pericytes, contribute to renal myofibroblast populations.
• Key mediators such as TGF-β1, mTOR, ROS, histone acetylation, microRNA, and lncRNA play crucial roles in myofibroblast activation.
• Various small molecules have demonstrated efficacy in suppressing myofibroblast activity and ameliorating RIF.

Conclusions:

• Understanding the multifaceted mechanisms of renal myofibroblast origin and activation is crucial for developing targeted RIF therapies.
• Small molecules targeting these pathways represent a promising therapeutic strategy for managing and potentially reversing RIF.
• This review provides insights into novel therapeutic targets and agents for combating RIF and improving patient outcomes.