Mechanism On The Treatment Of Autosomal Dominant Polycystic Kidney Disease With Rosiglitazone: Role Of P38MAPK Signalling Pathway

Objective: To investigate the role of P38 MAPK in the treatment for ADPKD with rosiglitazone Methods: The study is operated mainly in ADPKD kidney tissue. Protein distribution and staining changes are observed by immunity chemistry.Protein and mRNA expression are detected by western blot and RT-PCR. Activity of NF-κB is determined by relative luciferase activity of reporter gene.Intracellular calcium is detected by confocal laser microscopy.Results:1)The expression distribution and expression changes of P38,phospho-P38 and NF-κB in ADPKD kidney tissue are coincident.2)Rosiglitazone can reduce TGF-β1,MCP-1 and NF-κB expression/activity in MDCK cell through downregulating P38 activation and expression.3) PPARγantagonist does not all inhibit the reduction by rosiglitazone.4) Confocal laser microscopy discovers rosiglitazone of low dose have no effect on intracellular calcium and rosiglitazone of high dose (100umol/L and 200umol/L) can elevate intracellular calcium. Conclusions: Rosiglitazone possibly can reduce P38 and its downstream factor expression/ activity, then relieve inflammation response and interstitial fibrosis.The above effect of rosiglitazone is calcium -independent and in part PPARγ-independent.Our studies find rosiglitazone of high dose can elevate intracellular calcium,which possibly play essential roles in fluid retention induced by rosiglitazone.