title: Angiopoietin-1 attenuates angiotensin II-induced ER stress in glomerular endothelial cells via a Tie2 receptor/ERK1/2-p38 MAPK-dependent mechanism.
abstract: Research has indicated that endoplasmic reticulum (ER) stress in endothelial cells affects vascular pathologies and induces cellular dysfunction and apoptosis. Angiopoietin1 (Angpt1) has been shown to have therapeutic potential in some vascular diseases, including chronic kidney disease. This study showed that Angpt1 is a powerful factor that attenuated ER stress-induced cellular dysfunction and apoptosis in glomerular endothelial cells (GEnCs). Furthermore, Angpt1 significantly decreased the angiotensin II (Ang II)-induced expression of the ER stress response proteins GRP78, GRP94, p-PERK and CHOP. These results suggest that the Angpt1-mediated cellular protection may occur downstream of the ER stress response. In addition, both specific inhibitors and siRNAs for Tie2 reversed these changes, implying the importance of Tie2 receptor activation in the signalling pathways that prevent ER stress. The protective effects of Angpt1 are related to the activation of two downstream signalling pathways, ERK1/2 and p38 MAPK. The inhibition of these pathways with specific inhibitors, PD98059 and SB203580, respectively, partially increased the expression of chaperones that assist in folding proteins in the ER and reduce the protective effects of Angpt1. In conclusion, Angpt1 attenuated ER stress-induced cellular dysfunction and apoptosis via the Tie2 receptor/ERK1/2-p38 MAPK pathways in GEnCs. This study may provide insights into a novel underlying mechanism and a strategy for alleviating ER stress-induced injury.
authors.affiliation: Division of Nephrology, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Bi
authors.affiliation: Division of Nephrology, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Niu
authors.affiliation: Division of Nephrology, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.affiliation: Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Minmin
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Division of Nephrology, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China. Electronic address: minym@163.com.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China. Electronic address: yonggu@vip.163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D042683:Angiopoietin-1 / Q000494:pharmacology*; D000804:Angiotensin II / Q000009:adverse effects*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D042783:Endothelial Cells / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D006360:Heat-Shock Proteins / Q000378:metabolism; D007678:Kidney Glomerulus / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000378:metabolism*; D051742:Transcription Factor CHOP / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D042683:Angiopoietin-1; D015415:Biomarkers; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D000804:Angiotensin II; D051742:Transcription Factor CHOP; D009569:Nitric Oxide; D042787:Receptor, TIE-2; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Angiopoietins; Apoptosis; Cellular dysfunction; ER stress; MAPK pathway; Tie2