Role of Circadian Transcription Factor Rev-Erb in Metabolism and Tissue Fibrosis

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Raza G. S., Sodum N., Kaya Y., Herzig K.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, cilt.23, sa.21, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 23 Sayı: 21
  • Basım Tarihi: 2022
  • Doi Numarası: 10.3390/ijms232112954
  • Dergi Adı: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Anahtar Kelimeler: circadian rhythm, metabolism, transcription factor, Rev-Erb, fibrosis, GROWTH-FACTOR-BETA, CLOCK GENE-EXPRESSION, TUMOR-NECROSIS-FACTOR, HUMAN ADIPOSE-TISSUE, NUCLEAR RECEPTOR, EXTRACELLULAR-MATRIX, SKELETAL-MUSCLE, PULMONARY INFLAMMATION, MOLECULAR-MECHANISMS, INSULIN-RESISTANCE
  • Marmara Üniversitesi Adresli: Evet

Özet

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-kappa B 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.