University of Oulu

Raza GS, Sodum N, Kaya Y, Herzig K-H. Role of Circadian Transcription Factor Rev-Erb in Metabolism and Tissue Fibrosis. International Journal of Molecular Sciences. 2022; 23(21):12954.

Role of circadian transcription factor Rev-Erb in metabolism and tissue fibrosis

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Author: Raza, Ghulam Shere1; Sodum, Nalini1; Kaya, Yagmur2;
Organizations: 1Research Unit of Biomedicine, Medical Research Center, Faculty of Medicine, University of Oulu, 90220 Oulu, Finland
2Department of Nutrition and Dietetics, Faculty of Health Sciences, Marmara University, 34854 Istanbul, Turkey
3Oulu University Hospital, University of Oulu, 90220 Oulu, Finland
4Pediatric Gastroenterology and Metabolic Diseases, Pediatric Institute, Poznan University of Medical Sciences, 60-572 Poznań, Poland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.8 MB)
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Language: English
Published: Multidisciplinary Digital Publishing Institute, 2022
Publish Date: 2023-07-04


Circadian rhythms significantly affect metabolism, and their disruption leads to cardiometabolic diseases and fibrosis. The clock repressor Rev-Erb is mainly expressed in the liver, heart, lung, adipose tissue, skeletal muscles, and brain, recognized as a master regulator of metabolism, mitochondrial biogenesis, inflammatory response, and fibrosis. Fibrosis is the response of the body to injuries and chronic inflammation with the accumulation of extracellular matrix in tissues. Activation of myofibroblasts is a key factor in the development of organ fibrosis, initiated by hormones, growth factors, inflammatory cytokines, and mechanical stress. This review summarizes the importance of Rev-Erb in ECM remodeling and tissue fibrosis. In the heart, Rev-Erb activation has been shown to alleviate hypertrophy and increase exercise capacity. In the lung, Rev-Erb agonist reduced pulmonary fibrosis by suppressing fibroblast differentiation. In the liver, Rev-Erb inhibited inflammation and fibrosis by diminishing NF-κB activity. In adipose tissue, Rev- Erb agonists reduced fat mass. In summary, the results of multiple studies in preclinical models demonstrate that Rev-Erb is an attractive target for positively influencing dysregulated metabolism, inflammation, and fibrosis, but more specific tools and studies would be needed to increase the information base for the therapeutic potential of these substances interfering with the molecular clock.

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Series: International journal of molecular sciences
ISSN: 1661-6596
ISSN-E: 1422-0067
ISSN-L: 1661-6596
Volume: 23
Issue: 21
Article number: 12954
DOI: 10.3390/ijms232112954
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3111 Biomedicine
Copyright information: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (