The role of AdipoR1 and AdipoR2 in liver fibrosis

Alzahrani, Badr, Iseli, Tristan, Ramezani-Moghadam, Mehdi, Ho, Vikki, Wankell, Miriam, Sun, Eun Jin, Qiao, Liang, George, Jacob, and Hebbard, Lionel W. (2018) The role of AdipoR1 and AdipoR2 in liver fibrosis. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1864 (3). pp. 700-708.

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Abstract

Activation of the adiponectin (APN) signaling axis retards liver fibrosis. However, understanding of the role of AdipoR1 and AdipoR2 in mediating this response is still rudimentary. Here, we sought to elucidate the APN receptor responsible for limiting liver fibrosis by employing AdipoR1 and AdipoR2 knock-out mice in the carbon tetrachloride (CCl4) model of liver fibrosis. In addition, we knocked down receptor function in primary hepatic stellate cells (HSCs) in vitro. Following the development of fibrosis, AdipoR1 and AdipoR2 KO mice had no quantitative difference in fibrosis by Sirius red staining. However, AdipoR2 KO mice had an enhanced fibrotic signature with increased Col1-α1, TGFß-1, TIMP-1, IL-10, MMP-2 and MMP-9. Knockdown of AdipoR1 or AdipoR2 in HSCs followed by APN treatment demonstrated that AdipoR1 and AdipoR2 did not affect proliferation or TIMP-1 gene expression, while AdipoR2 modulated Col1-α1 and α-SMA gene expression, HSC migration, and AMPK activity. These finding suggest that AdipoR2 is the major APN receptor on HSCs responsible for mediating its anti-fibrotic effects.

Item ID: 51791
Item Type: Article (Research - C1)
ISSN: 0925-4439
Keywords: liver fibrosis; adipoR1; adipoR2
Funders: National Health and Medical Research Council (NHMRC), Cancer Council New South Wales and Queensland (CC), James Cook University (JCU), Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney
Projects and Grants: NHMRC Program grant APP1053206, NHMRC Project Grant APP1047417, NHMRC Project Grant APP632630, NHMRC project grant 1049857, NHMRC Project Grant APP1006200, CC Project grant APP1070076, CC Project grant APP1069733, CC Project grant APP1123436, JCU Development Grant 94066
Date Deposited: 18 Dec 2017 23:56
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110307 Gastroenterology and Hepatology @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920105 Digestive System Disorders @ 100%
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