Published on: June 2025
Indian Journal of Pharmacy Practice, 2025; 18(4):390-398.
Review Article| doi: 10.5530/ijopp.20250293
Authors and affiliation (s):
Sayyed Mateen, Aafreen Qureshi*, Amit Sharma, Vikas Gupta
Department of Pharmacology, Oriental College of Pharmacy, University of Mumbai, Sanpada, Navi Mumbai, Maharashtra, INDIA.
ABSTRACT
The circadian cellular clock partially reduces macrophage inflammatory response by interacting with the nuclear receptor Rev-erbα. Disruption of circadian rhythm can result in diabetes, metabolic issues and fibrosis. Rev-Erb clock repressor is expressed in the brain, skeletal muscles, liver, heart & lungs. Rev-Erb reduces lung fibrosis and inflammation by acting on NF-κB. Agonists of Rev-Erb lead to a decrease in fat mass specifically in adipose tissue. These agonists also reduce pulmonary fibrosis by preventing myofibroblast differentiation in the lung. A decrease in REV-ERBα levels makes the lungs more sensitive to pro-fibrotic triggers, worsening fibrosis progression. Overproduction of collagen as well as lysyl oxidase due to TGFβ can be stopped by GSK4112, an agonist of Rev-erbα in human lung fibroblasts while an opposite impact is shown by the antagonist. Progression of Lung Adenocarcinoma is contributed by the downregulation of REV-ERBα. Agonists of REV-ERBα such as SR9009 and GSK4112, have therapeutic potential in reducing lung inflammation caused by cigarette smoke-induced COPD. GSK4112 (agonist) and GSK1362 (inverse agonist) target REV-ERBα to reduce pulmonary inflammation, with GSK1362 offering superior efficacy by stabilizing REV-ERBα protein. Based on these findings, there is hope for the therapeutic development of Rev-Erbα agonists for lung fibrosis, thus, further research and clinical trial.
Keywords:Circadian rhythm, COPD, Fibrosis, Inflammation, Rev-Erbα.