Regulating the Clock: REV-ERB Agonists as Promising Therapeutic Agents

Rev-erbα agonists suppresses TGFβ1-induced fibroblast-to-myofibroblast transition and pro-fibrotic phenotype in human lung fibroblasts

“…Novel therapies to treat pulmonary fibrosis and other fibrotic diseases are an unmet clinical need that has to be addressed. Emerging studies using preclinical models, in vitro and in vivo, demonstrated the potential of circadian clock-based therapeutics such as Rev-erbα agonists that directly or indirectly target TGFβ signaling to mitigate the progression of PF [ 9 , 10 , 16 ].…”

“…that activate Rev-erbα promote the suppression of Rev-erbα-dependent target genes, and Rev-erbα antagonist (SR8278) inhibits the Rev-erbα-mediated suppression of target genes [ 11 , 12 ]. Earlier reports have demonstrated Rev-erbα agonists as a novel therapeutic agent that can modulate cellular and physiological processes linked to inflammation and metabolism [ 11 , 13 – 16 ]. Clock mutant ( Clock ∆19 ) and Rev-erbα fibroblast-specific knockout (KO) mice demonstrate worse fibrosis after bleomycin-induced lung injury.…”