title: Uric acid-induced endoplasmic reticulum stress triggers phenotypic change in rat glomerular mesangial cells.
abstract: OBJECTIVE
  The aim of this study was to explore the contribution and the mechanism of uric acid (UA) to phenotypic change in rat glomerular mesangial cells.
  
  
  METHODS
  Rat glomerular mesangial cells (HBZY-1) were exposed to UA (0.05 mmol/L to 0.4 mmol/L) for 24 h to 48 h. Subsequently, 4-phenyl butyric acid (4-PBA) (5 mg/dL) was added and 48 h incubation was performed. HBZY-1 cells exposed to UA (0.4 mmol/L) were incubated for 48 h. After incubation, the cells were examined under an inverted microscope and transmission electron microscope to observe their morphologies and the expressions of α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), fibronectin (FN), glucose regulated protein 78 (GRP78), and the protein disulfide isomerase (PDI) proteins and mRNA in the HBZY-1 cells were measured by Western blot and reversed transcription-polymerase chain reaction.
  
  
  RESULTS
  HBZY-1 cultured in UA showed evident morphological changes under transmission electron microscopy. The soluble UA stimulated the upregulation of the α-SMA, TGF-β1 and FN mRNA and proteins in a concentration- and time-dependent manner. UA-induced endoplasmic reticulum (ER) stress, as evidenced by the upregulation of the mRNA and protein expressions of GRP78 and PDI. However, the upregulation was reverted by 4-PBA, an inhibitor of ER stress.
  
  
  CONCLUSIONS
  Uric acid induces phenotypic change in HBZY-1 cells. ER stress plays a central role in UA-induced phenotypic transformation in vitro. 4-PBA may be beneficial in attenuating UA-induced glomerular injury.
authors.affiliation: Medicine School of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Zhao
authors.forename: Shaoli
authors.initials: S
authors.lastname: Cheng
authors.forename: Xinyang
authors.initials: X
authors.lastname: Wang
authors.forename: Yaning
authors.initials: Y
authors.lastname: Hao
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D048430:Cell Shape / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010641:Phenotype; D010654:Phenylbutyrates / Q000494:pharmacology; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014527:Uric Acid / Q000494:pharmacology*; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D000199:Actins; D005353:Fibronectins; D006360:Heat-Shock Proteins; D010654:Phenylbutyrates; D019704:Protein Disulfide-Isomerases; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D014527:Uric Acid; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C508962:Tgfb1 protein, rat; C498862:Acta2 protein, rat; C075773:4-phenylbutyric acid
keywords: 4-phenyl butyric acid; endoplasmic reticulum stress; phenotypic change; rat glomerular mesangial cell; uric acid