title: Lipid accumulation is ahead of epithelial-to-mesenchymal transition and therapeutic intervention by acetyl-CoA carboxylase 2 silence in diabetic nephropathy.
abstract: OBJECTIVE
  The study investigated the relationship between epithelial-to-mesenchymal transition (EMT) and lipotoxicity in diabetic nephropathy as well as the protective effect of acetyl-CoA carboxylase 2 (ACC2) silence.
  
  
  METHODS
  High glucose (30mmol/L) cultured human proximal tubular epithelial cells (HK-2 cells) were used. Triglyceride content, fatty acid β-oxidation rate, malonyl CoA content, and marker proteins of EMT, including E-cadherin (E-cad), α-smooth muscle actin (α-SMA) and transforming grow factor-β (TGF-β), were assessed. Silence of ACC2 was achieved by ACC2-shRNA lentivirus transfection.
  
  
  RESULTS
  In cultured human proximal tubular cells, high glucose induced fatty acid deposit before phenotypical and morphological changes of EMT. At 48h, more triglyceride content, more malonyl CoA content and lower fatty acid β-oxidation rate were detected. However, increased expression of TGF-β, accompanied by loss of E-cad and acquisition of α-SMA, was observed at 98h but not at 48h. The silence of ACC2 in HK-2 cells led to restored cell morphology with less lipid deposition and less malonyl-CoA content, which resulted from faster β-oxidation rate.
  
  
  CONCLUSIONS
  The progress of lipotoxicity participates in the development of diabetic nephropathy in early stage before EMT. The manipulation of lipid metabolism might act as a promising therapeutic intervention for diabetic nephropathy.
authors.affiliation: Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: School of Medicine, Shandong University, Jinan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Center Lab of Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xin
authors.affiliation: Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, China.
authors.forename: Liyong
authors.initials: L
authors.lastname: Chen
authors.affiliation: School of Medicine, Shandong University, Jinan, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Zhimei
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, China; Department of Respiratory Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. Electronic address: 15168888626@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, China. Electronic address: wanyanshaoqiang@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wan
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics*; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects / Q000235:genetics; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000628:therapy*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005227:Fatty Acids / Q000009:adverse effects / Q000378:metabolism; D020868:Gene Silencing / Q000502:physiology*; D015316:Genetic Therapy / Q000379:methods*; D005947:Glucose / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D008316:Malonyl Coenzyme A / Q000378:metabolism; D014280:Triglycerides / Q000009:adverse effects / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D014280:Triglycerides; D008316:Malonyl Coenzyme A; C520105:ACACB protein, human; D000103:Acetyl-CoA Carboxylase; D005947:Glucose
keywords: Diabetes; Epithelial to mesenchymal transition; Lipotoxicity; Proximal tubular epithelial cells; β-oxidation