title: Adiponectin attenuates Ang Ⅱ-induced TGFβ1 production in human mesangial cells via an AMPK-dependent pathway.
abstract: Glomerulosclerosis is a key element in end-stage renal failure. Angiotensin II (Ang II) plays an important role in modulating cell growth and extracellular matrix (ECM) synthesis and degradation. Adiponectin, a protein derived from adipocytes, is primarily involved in regulating glucose levels and fatty acid break down. It has recently been shown to have antiatherosclerotic and anti-inflammatory properties. However, the role of adiponectin as a renoprotective agent has not been fully explored. We herein examine the effect of adiponectin on Ang II-induced TGFβ1 and ECM production in human renal mesangial cells (HRMCs) and explore the signaling pathway involved. In this study, we found that both adiponectin receptor 1 and adiponectin receptor 2 are expressed in HRMCs. Adiponectin (10 μg/mL) attenuated the stimulatory effect of Ang II on TGF-β1 and fibronectin. Furthermore, adiponectin activated the AMP-activated protein kinase (AMPK), and the AMPK-specific inhibitor (compound C) blocked AMPK activation. We also determined that compound C blocked the inhibitory effect of adiponectin on Ang II-stimulated TGFβ1 and fibronectin production. In summary, these results demonstrate that adiponectin suppresses Ang II-induced synthesis of ECM in mesangial cells via activation of the AMPK pathway. Based on our data, we suggest that this mechanism could delay the progression of kidney disease.
authors.affiliation: Department of Nephrology, China-Japan Friendship Hospital, Health Ministry of China, Beijing, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Tan
authors.affiliation: Department of Nephrology, China-Japan Friendship Hospital, Health Ministry of China, Beijing, People's Republic of China.
authors.forename: Gongyao
authors.initials: G
authors.lastname: Tang
authors.affiliation: Center Of Kidney Disease, An Zhen Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Rui
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D052242:Adiponectin / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D002460:Cell Line; D005353:Fibronectins / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D054419:Receptors, Adiponectin / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis*
chemical_list: D052242:Adiponectin; D005353:Fibronectins; D054419:Receptors, Adiponectin; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D055372:AMP-Activated Protein Kinases
keywords: AMPK; TGF-β1; adiponectin; angiotensin Ⅱ; fibronectin; human renal mesangial cell