title: Involvement of endoplasmic reticulum stress in albuminuria induced inflammasome activation in renal proximal tubular cells.
abstract: Albuminuria contributes to the progression of tubulointerstitial fibrosis. Although it has been demonstrated that ongoing albuminuria leads to tubular injury manifested by the overexpression of numerous proinflammatory cytokines, the mechanism remains largely unknown. In this study, we found that the inflammasome activation which has been recognized as one of the cornerstones of intracellular surveillance system was associated with the severity of albuminuria in the renal biopsies specimens. In vitro, bovine serum albumin (BSA) could also induce the activation of NLRP3 inflammasome in the cultured kidney epithelial cells (NRK-52E). Since there was a significant overlap of NLRP3 with the ER marker calreticulin, the ER stress provoked by BSA seemed to play a crucial role in the activation of inflammasome. Here, we demonstrated that the chemical chaperone taurine-conjugated ursodeoxycholic acid (TUDCA) which was proved to be an enhancer for the adaptive capacity of ER could attenuate the inflammasome activation induced by albuminuria not only in vitro but also in diabetic nephropathy. Taken together, these data suggested that ER stress seemed to play an important role in albuminuria-induced inflammasome activation, elimination of ER stress via TUDCA might hold promise as a novel avenue for preventing inflammasome activation ameliorating kidney epithelial cells injury induced by albuminuria.
authors: Center for Kidney Disease, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors: Li
authors: L
authors: Fang
authors: Da
authors: D
authors: Xie
authors: Xian
authors: X
authors: Wu
authors: Hongdi
authors: H
authors: Cao
authors: Weifang
authors: W
authors: Su
authors: Junwei
authors: J
authors: Yang
mesh_terms: D000419:Albuminuria / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D037282:Calreticulin / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000235:genetics*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D058847:Inflammasomes / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D051381:Rats; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*
chemical_list: D037282:Calreticulin; D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D012710:Serum Albumin, Bovine; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine
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