TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000225831
  • Gene Name:CCL2
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:NA
  • 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:patients tissues

Other information

  • Title:Rapamycin attenuates aldosterone-induced tubulointerstitial inflammation and fibrosis
  • Journal:Cellular Physiology And Biochemistry
  • Published:2015
  • PubMed ID:25547416
  • Abstract:Background/aim:Aldosterone (Aldo), a mediator of kidney fibrosis, is implicated in the pathogenesis of chronic kidney diseases (CKD). The aim of this study was to evaluate the regulatory role of rapamycin (Rap) in Aldo-induced tubulointerstitial inflammation and fibrosis. Methods:Uninephrectomized, Sprague-Dawley rats were given 1% NaCl (salt) to drink and were randomized to receive treatment for 28 days as follows: vehicle infusion (control), 0.75 μg/h Aldo subcutaneous infusion, or Aldo infusion plus 1 mg/kg/day of Rap by intraperitoneal injection. The effect of Rap on Aldo-induced fibrosis and renal inflammation was investigated using Masson＇s technique, immunohistochemistry, and western blotting. The effects of Rap on the Aldo-induced epithelial-mesenchymal transition (EMT) process and on TNF-α mRNA expression and secretion in cultured HK-2 cells were investigated by immunofluorescent staining, western blot, qRT-PCR and ELISA. Results:An in vivo study indicated that signaling by the mammalian target of Rap (mTOR) was activated in rats in the Aldo group compared to controls, as indicated by up-regulated expression of p-mTOR and p-S6K. In addition, the inflammatory response increased, as evidenced by increases in inflammatory markers (MCP-1, ICAM-1, F4/80), and the accumulation of extracellular matrix (ECM), as indicated by increased collagen I and fibronectin expression and pro-fibrogenic gene (PAI-1 and TGF-β1) expression. These changes were attenuated by Rap treatment. An in vitro study showed that Rap significantly suppressed the Aldo-induced EMT process and TNF-α mRNA expression and secretion in cultured HK-2 cells. Conclusions:Rap can ameliorate tubulointerstitial inflammation and fibrosis by blocking mTOR signaling. Tubular cells may be a major cell type involved in this physiologic process.
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