title: Inhibitory effects of dimethyl α-ketoglutarate in hepatic stellate cell activation.
abstract: OBJECTIVE
  The activation of Hepatic stellate cell (HSC) is a pivotal event in the initiation and progression of hepatic fibrosis and a major source of collagen deposition. A recent study found that autophagy fuels the HSC activation. α-ketoglutarate (AKG), an intermediate in the Kerbs CYCLE, has been shown to regulate the level of autophagy. In this study, we aim to investigate the potential effect of dimethyl α-ketoglutarate (DMKG), a membrane-permeable esters of AKG, on the activation of HSC.
  
  
  METHODS
  HSC and hepatocyte cell lines were treated with DMKG at gradient concentrations, MTT assay was used to assess the cell viability. Concentrations of DMKG that did not affect the cell survival were added to the culture media of HSC cells. Real-time PCR and western blot analysis was carried out to evaluate the expression of fibrogenic genes in HSC after culture for 24 hours.
  
  
  RESULTS
  Low dose of DMKG had little cytotoxicity to both HSCs and hepatocytes, while HSCs were more vulnerable to high dose of DMKG than hepatocytes. More importantly, DMKG inhibited the expression of α-SMA and collagen I significantly in HSCs detected by real-time PCR and western blot analysis at the concentrations that didn't decrease cell viability.
  
  
  CONCLUSIONS
  DMKG has a significant role of inhibiting the activation of HSC and may attenuate hepatic fibrosis safely.
authors.affiliation: Department of Geriatric Gastroenterology, Qilu Hospital of Shandong University Jinan, Shandong, China ; Key Laboratory of Cardiovascular Remodeling, Qilu Hospital of Shandong University Jinan, Shandong, China.
authors.forename: Jianjian
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Geriatric Gastroenterology, Qilu Hospital of Shandong University Jinan, Shandong, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Peng
authors.affiliation: Department of Geriatric Gastroenterology, Qilu Hospital of Shandong University Jinan, Shandong, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Department of Geriatric Gastroenterology, Qilu Hospital of Shandong University Jinan, Shandong, China.
authors.forename: Ruibing
authors.initials: R
authors.lastname: Cui
authors.affiliation: Department of Geriatric Gastroenterology, Qilu Hospital of Shandong University Jinan, Shandong, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000494:pharmacology*; D008103:Liver Cirrhosis / Q000378:metabolism; D051381:Rats
chemical_list: D007656:Ketoglutaric Acids; C541783:dimethyl alpha-ketoglutarate
keywords: Dimethyl α-ketoglutarate; Hepatic fibrosis; autophagy; extracellular matrix; hepatic stellate cell