title: Angiotensin-(1-7) attenuates high glucose-induced proximal tubular epithelial-to-mesenchymal transition via inhibiting ERK1/2 and p38 phosphorylation.
abstract: OBJECTIVE
  The kidney is an important target for both Angiotensin II and angiotensin-(1-7) [Ang-(1-7)] in the renin-angiotensin system. However, the renal function of Ang-(1-7) remains unclear. This study is aimed at investigating the effect of Ang-(1-7) on high glucose-induced epithelial to mesenchymal transition (EMT) in cultured renal epithelial cells.
  
  
  METHODS
  Cultured renal epithelial (NRK-52E) cell line was used in the experiment. Fluorescence immunocytochemistry was performed to observe α-smooth muscle actin (α-SMA). Real-time PCR and Western blot were used to determine mRNA and protein levels. Enzyme-linked immunosorbent assay was used to measure the concentration of transforming growth factor-β1 (TGF-β1) in the culture media.
  
  
  RESULTS
  High glucose-induced decreased in both angiotensin-converting enzyme-related carboxypeptidase (ACE2) and Mas mRNA levels. Meanwhile, high glucose induced increases in α-SMA and vimentin, decreases in E-cadherin, elevations in TGF-β1 and fibronectin secretions. Ang-(1-7) partially reversed high glucose-induced changes in α-SMA, vimentin, E-cadherin, TGF-β1 and fibronectin. High glucose stimulated ERK, p38 and JNK phosphorylation and Ang-(1-7) reversed the changes in ERK and p38 but not JNK phosphorylation.
  
  
  CONCLUSIONS
  Inhibition and insufficiency in ACE2-Ang-(1-7)-Mas axis under high glucose condition participate EMT. Supplementation of Ang-(1-7) attenuates high glucose-induced EMT. ERK and p38 intracellular signaling pathways, not JNK, mediate the effect of Ang-(1-7) on EMT.
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University Shanghai 200032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Hong
authors.initials: H
authors.lastname: Xue
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Ni
authors.forename: Tai
authors.initials: T
authors.lastname: Yao
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Chen
authors.initials: C
authors.lastname: Yu
authors.forename: Limin
authors.initials: L
authors.lastname: Lu
mesh_terms: D000199:Actins / Q000187:drug effects; D000704:Analysis of Variance; D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000502:physiology*; D005453:Fluorescence; D005947:Glucose; D007150:Immunohistochemistry; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000199:Actins; D000803:Angiotensin I; D017931:DNA Primers; D005947:Glucose; D010446:Peptide Fragments; C498862:Acta2 protein, rat; C118790:angiotensin I (1-7)