TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000225831
  • Gene Name:CCL2
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:PCR
  • mRNA Pathway:MTOR pathway
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB00877
  • Drug Name:Sirolimus
  • Drug Method:down-regulated the gene expression

Disease basic infommation

  • Disease:chronic kidney disease
  • Tissue:tissues

Other information

  • Title:Lipopolysaccharide Induces Chronic Kidney Injury and Fibrosis through Activation of mTOR Signaling in Macrophages
  • Journal:American Journal of Nephrology
  • Published:2015
  • PubMed ID:26517816
  • Abstract:Background:Septic kidney injury is one of the most common complications in critically ill patients with a high risk of developing chronic kidney disease (CKD). Emerging data indicate that mammalian target of rapamyci (mTOR) signaling plays a major role in septic inflammation by regulating the immune response of macrophage. This study was designed to evaluate the role of mTOR signaling in kidney macrophages during endotoxemia-induced chronic kidney injury and subsequent fibrogenesis. Methods:Male C57BL/6 mice were used for all animal studies (n=9 for each group). Lipopolysaccharide (LPS) was injected intraperitoneally (1 mg/kg) every 2 days to induce persistent endotoxemia. Rapamycin (1 mg/kg·day) was administered to a subgroup of mice 1 day prior to LPS treatment and continued to termination of the experiment. In ex-vivo experiment, RAW264.7 cells were cultured and treated with LPS (2 μg/ml) for 48 h while a subgroup of cells were incubated in the presence of rapamycin (50 nmol) for 2 h. Results:Continuous administration of LPS resulted in progressive macrophage infiltration, tubular injury and collagen deposition in mice kidneys. Rapamycin markedly ameliorated LPS-induced kidney pathological changes. Expression of pS6K was rarely observed in normal kidney macrophages, but significantly increased with time by LPS treatment. In ex-vivo study, LPS induced prominent production of IL-1β and MCP-1 in cultured RAW264.7 cells, which was significantly suppressed by rapamycin. Conclusion:Taken together, our findings show that endotoxemia results in activation of mTOR signaling in macrophages, leading to progressive kidney inflammatory injuries and subsequent fibrosis. Our study may reveal a mechanism involved in the development of sepsis-associated CKD and kidney fibrosis.
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