| First Author | Komada T | Year | 2014 |
| Journal | Am J Pathol | Volume | 184 |
| Issue | 5 | Pages | 1287-98 |
| PubMed ID | 24606883 | Mgi Jnum | J:208136 |
| Mgi Id | MGI:5561158 | Doi | 10.1016/j.ajpath.2014.01.014 |
| Citation | Komada T, et al. (2014) ASC in Renal Collecting Duct Epithelial Cells Contributes to Inflammation and Injury after Unilateral Ureteral Obstruction. Am J Pathol 184(5):1287-98 |
| abstractText | Inflammation plays a crucial role in the pathophysiological characteristics of chronic kidney disease; however, the inflammatory mechanisms underlying the chronic kidney disease process remain unclear. Recent evidence indicates that sterile inflammation triggered by tissue injury is mediated through a multiprotein complex called the inflammasome. Therefore, we investigated the role of the inflammasome in the development of chronic kidney disease using a murine unilateral ureteral obstruction (UUO) model. Inflammasome-related molecules were up-regulated in the kidney after UUO. Apoptosis-associated speck-like protein containing a caspase recruitment domain deficiency significantly reduced inflammatory responses, such as inflammatory cell infiltration and cytokine expression, and improved subsequent renal injury and fibrosis. Furthermore, apoptosis-associated speck-like protein containing a caspase recruitment domain was specifically up-regulated in collecting duct (CD) epithelial cells of the UUO-treated kidney. In vitro experiments showed that extracellular adenosine triphosphate (ATP) induced inflammasome activation in CD epithelial cells through P2X7-potassium efflux and reactive oxygen species-dependent pathways. These results demonstrate the molecular basis for the inflammatory response in the process of chronic kidney disease and suggest the CD inflammasome as a potential therapeutic target for preventing chronic kidney disease progression. |
