title: AMP-activated protein kinase alleviates extracellular matrix accumulation in high glucose-induced renal fibroblasts through mTOR signaling pathway.
abstract: OBJECTIVE
  Extracellular matrix accumulation contributes significantly to the pathogenesis of diabetic nephropathy. Although AMP-activated protein kinase (AMPK) has been found to inhibit extracellular matrix synthesis by experiments in vivo and vitro, its role in alleviating the deposition of extracellular matrix in renal interstitial fibroblasts has not been well defined.
  
  
  METHODS
  Currently, we conducted this study to investigate the effects of AMPK on high glucose-induced extracellular matrix synthesis and involved intracellular signaling pathway by using western blot in the kidney fibroblast cell line (NRK-49f).
  
  
  RESULTS
  Collagen IV protein levels were significantly increased by high glucose in a time-dependent manner. This was associated with a decrease in Thr72 phosphorylation of AMPK and an increase in phosphorylation of mTOR on Ser2448. High glucose-induced extracellular matrix accumulation and mTOR activation were significantly inhibited by the co-treatment of rAAV-AMPKα1(312) (encoding constitutively active AMPKα1) whereas activated by r-AAV-AMPKα1D157A (encoding dominant negative AMPKα1). In cultured renal fibroblasts, overexpression of AMPKα1D157A upregulated mTOR signaling and matrix synthesis, which were ameliorated by co-treatment with the inhibitor of mTOR, rapamycin.
  
  
  CONCLUSIONS
  Collectively, these findings indicate that AMPK exerts renoprotective effects by inhibiting the accumulation of extracellular matrix through mTOR signaling pathway.
authors.affiliation: Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Luo
authors.forename: Lingyan
authors.initials: L
authors.lastname: Deng
authors.forename: Laxmi Pangeni
authors.initials: LP
authors.lastname: Lamsal
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Xu
authors.forename: Cheng
authors.initials: C
authors.lastname: Xiang
authors.forename: Liming
authors.initials: L
authors.lastname: Cheng
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002460:Cell Line; D024141:Collagen Type IV / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D009154:Mutation; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D024141:Collagen Type IV; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C568305:Prkaa1 protein, rat; D000103:Acetyl-CoA Carboxylase; D005947:Glucose