title: Angiotensin-(1-7) attenuates damage to podocytes induced by preeclamptic serum through MAPK pathways.
abstract: The underlying mechanisms of proteinuria, a main characteristic of preeclampsia (PE), have not yet been fully elucidated. Evidence indicates that the renin-angiotensin system (RAS) is involved in the pathogenesis of this disease, including decreased angiotensin-(1-7) [Ang-(1-7)] levels in the circulation and urine. In the present study, we examined the damage to podocytes induced by preeclamptic serum and the effects of Ang-(1-7) on podocytes treated with preeclamptic serum, as well as the underlying mechanisms. The podocytes were incubated with serum obtained from women with PE or with serum from women with normal pregnancies for different periods of time. Cell viability was determined by CCK-8 assay. The cells were treated with various concentrations of Ang-(1-7) and A779 [an (Ang-(1-7) antagonist]. The effects of Ang-(1-7) on the expression of podocyte-specific proteins [nephrin, Wilms tumor‑1 (WT-1) and podocin] and the phosphorylation of mitogen-activated protein kinases (MAPKs) were investigated by western blot analysis. Changes in F-actin rearrangement were determined by immunofluorescence. Podocyte apoptosis was determined by flow cytometry. The results revealed that in the cultured podocytes incubated with preeclamptic serum, there was a decrease in the expression of podocyte-specific proteins (nephrin and WT-1 but not podocin), a rearrangement of F-actin and apoptosis compared with the control group. However, treatment with Ang-(1-7) attenuated podocyte injury in the preeclamptic group, which may be mediated through the downregulation of MAPK (p38, ERK1/2 and JNK) phosphorylation. Thus, our data suggest that Ang-(1-7) plays a protective role in PE through the downregulation of MAPK phosphorylation.
authors.affiliation: Division of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, P.R. China.
authors.forename: Jimei
authors.initials: J
authors.lastname: Tian
authors.affiliation: Division of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, P.R. China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Division of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, P.R. China.
authors.forename: Yunjiao
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Division of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Division of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, P.R. China.
authors.forename: Sheran
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Gynaecology and Obstetrics, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, P.R. China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai, P.R. China.
authors.forename: Zhongdong
authors.initials: Z
authors.lastname: Qiao
authors.affiliation: Division of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, P.R. China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Niu
authors.affiliation: Division of Nephrology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008565:Membrane Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D050199:Podocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D011225:Pre-Eclampsia / Q000097:blood* / Q000201:enzymology*; D011247:Pregnancy; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
chemical_list: C092006:7-Ala-angiotensin (1-7); D000199:Actins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; C113267:nephrin; D000804:Angiotensin II; D000803:Angiotensin I; D020928:Mitogen-Activated Protein Kinases; C118790:angiotensin I (1-7)