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ASC in Renal Collecting Duct Epithelial Cells Contributes to Inflammation and Injury after Unilateral Ureteral Obstruction
- Source :
- The American Journal of Pathology. 184:1287-1298
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- 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 P2X 7 -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.
- Subjects :
- Male
Pathology
medicine.medical_specialty
Apoptosis
Inflammation
Pathology and Forensic Medicine
Fibrosis
medicine
Extracellular
Animals
Kidney Tubules, Collecting
Caspase
Kidney
biology
urogenital system
business.industry
Epithelial Cells
Inflammasome
medicine.disease
Pathophysiology
CARD Signaling Adaptor Proteins
Mice, Inbred C57BL
medicine.anatomical_structure
biology.protein
Cytokines
medicine.symptom
Apoptosis Regulatory Proteins
business
Ureteral Obstruction
Kidney disease
medicine.drug
Subjects
Details
- ISSN :
- 00029440
- Volume :
- 184
- Database :
- OpenAIRE
- Journal :
- The American Journal of Pathology
- Accession number :
- edsair.doi.dedup.....5fb7817f51428b7991ace201b69d75a5