TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000264657
  • Gene Name:STAT3
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:qPCR
  • mRNA Pathway:JAK2-STAT1/STAT3 signaling pathway
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:Osthole
  • Drug Method:down-regulated the gene expression

Disease basic infommation

  • Disease:diabetic nephropathy
  • Tissue:tissue

Other information

  • Title:Effect of osthole on advanced glycation end products-induced renal tubular hypertrophy and role of klotho in its mechanism of action
  • Journal:Phytomedicine
  • Published:2019
  • PubMed ID:30668400
  • Abstract:Background:Osthole has been widely reported to have pharmacological activities such as anti-cancer, anti-inflammation and anti-hyperlipidemic effects. Klotho was identified as an anti-senescence protein in a variety of tissues. Loss of klotho has been associated with chronic kidney disease. However, potential roles and molecular events for osthole and klotho in diabetic nephropathy remain unclear. Purpose:In the current study, we undertook to study the effect of osthole on klotho expression in advanced glycation end products (AGE)-cultured human renal proximal tubular cells, and to investigate the molecular mechanisms of osthole and exogenous klotho against AGE-induced renal tubular hypertrophy. Methods:Cell viability was elucidated by MTT assay. Protein expression was measured by Western blotting. mRNA level was analyzed by real-time PCR. Cellular hypertrophy growth was evaluated by hypertrophy index. Relative cell size was detected by flow cytometry. Results:We found that raising the ambient AGE concentration causes a dose-dependent decrease in klotho synthesis. Osthole significantly increased AGE-inhibited klotho mRNA and protein expression. Osthole and exogenous klotho treatments significantly attenuated AGE-induced Janus kinase 2 (JAK2)-signal transducers and activators of transcription 1 (STAT1) and STAT3 activation. Moreover, protein levels of suppressor of cytokine signaling 1 (SOCS1) and SOCS3 were augmented by osthole and exogenous klotho. The abilities of osthole and exogenous klotho to reverse AGE-induced cellular hypertrophy were verified by the observation that osthole and exogenous klotho inhibited p21Waf1/Cip1/collagen IV/RAGE expression, total protein content, and cell size. Conclusion:Consequently, we found that osthole attenuated AGE-induced renal tubular hypertrophy via induction of klotho expression and suppression of the JAK2-STAT1/STAT3 signaling. These results also showed that klotho might be used as a unique molecular target for the treatment of diabetic nephropathy.
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