title: The emerging roles of β-arrestins in fibrotic diseases.
abstract: β-Arrestins and β-arrestin2 are important adaptor proteins and signal transduction proteins that are mainly involved in the desensitization and internalization of G-protein-coupled receptors. Fibrosis is characterized by accumulation of excess extracellular matrix (ECM) molecules caused by chronic tissue injury. If highly progressive, the fibrotic process leads to organ malfunction and, eventually, death. The incurable lung fibrosis, renal fibrosis and liver fibrosis are among the most common fibrotic diseases. Recent studies show that β-arrestins can activate signaling cascades independent of G-protein activation and scaffold many intracellular signaling networks by diverse types of signaling pathways, including the Hedgehog, Wnt, Notch and transforming growth factor-β pathways, as well as downstream kinases such as MAPK and PI3K. These signaling pathways are involved in the pathological process of fibrosis and fibrotic diseases. This β-arrestin-mediated regulation not only affects cell growth and apoptosis, but also the deposition of ECM, activation of inflammatory response and development of fibrotic diseases. In this review, we survey the involvement of β-arrestins in various signaling pathways and highlight different aspects of their regulation of fibrosis. We also discuss the important roles of β-arrestins in the process of fibrotic diseases by regulating the inflammation and deposit of ECM. It is becoming more evident that targeting β-arrestins may offer therapeutic potential for the treatment of fibrotic diseases.
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei 230032, China.
authors.forename: Yuan-jing
authors.initials: YJ
authors.lastname: Gu
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei 230032, China.
authors.forename: Wu-yi
authors.initials: WY
authors.lastname: Sun
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei 230032, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei 230032, China.
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Wu
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei 230032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D019390:Arrestins / Q000032:analysis / Q000276:immunology*; D002318:Cardiovascular Diseases / Q000276:immunology / Q000473:pathology*; D002319:Cardiovascular System / Q000276:immunology / Q000473:pathology; D005109:Extracellular Matrix / Q000276:immunology / Q000473:pathology; D005355:Fibrosis; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D007410:Intestinal Diseases / Q000276:immunology / Q000473:pathology*; D007422:Intestines / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008107:Liver Diseases / Q000276:immunology / Q000473:pathology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008171:Lung Diseases / Q000276:immunology / Q000473:pathology*; D015398:Signal Transduction; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D000071557:beta-Arrestins