NLRP3 Deficiency Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in a Mouse Unilateral Ureteral Obstruction Model of Chronic Kidney Disease
Background and Aims. The nucleotide-binding domain and leucine-rich repeat containing PYD-3 (NLRP3) inflammasome has been implicated in the pathogenesis of chronic kidney disease (CKD); however, its exact role in glomerular injury and tubulointerstitial fibrosis is still undefined. The present study...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2017/8316560 |
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| author | Honglei Guo Xiao Bi Ping Zhou Shijian Zhu Wei Ding |
| author_facet | Honglei Guo Xiao Bi Ping Zhou Shijian Zhu Wei Ding |
| author_sort | Honglei Guo |
| collection | DOAJ |
| description | Background and Aims. The nucleotide-binding domain and leucine-rich repeat containing PYD-3 (NLRP3) inflammasome has been implicated in the pathogenesis of chronic kidney disease (CKD); however, its exact role in glomerular injury and tubulointerstitial fibrosis is still undefined. The present study was performed to identify the function of NLRP3 in modulating renal injury and fibrosis and the potential involvement of mitochondrial dysfunction in the murine unilateral ureteral obstruction (UUO) model of CKD. Methods. Employing wild-type (WT) and NLRP3−/− mice with or without UUO, we evaluated renal structure, tissue injury, and mitochondrial ultrastructure, as well as expression of some vital molecules involved in the progression of fibrosis, apoptosis, inflammation, and mitochondrial dysfunction. Results. The severe glomerular injury and tubulointerstitial fibrosis induced in WT mice by UUO was markedly attenuated in NLRP3−/− mice as evidenced by blockade of extracellular matrix deposition, decreased cell apoptosis, and phenotypic alterations. Moreover, NLRP3 deletion reversed UUO-induced impairment of mitochondrial morphology and function. Conclusions. NLRP3 deletion ameliorates mitochondrial dysfunction and alleviates renal fibrosis in a murine UUO model of CKD. |
| format | Article |
| id | doaj-art-980ffa10f7c94756bf09f97d0a59e2c1 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-980ffa10f7c94756bf09f97d0a59e2c12025-02-03T05:54:15ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/83165608316560NLRP3 Deficiency Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in a Mouse Unilateral Ureteral Obstruction Model of Chronic Kidney DiseaseHonglei Guo0Xiao Bi1Ping Zhou2Shijian Zhu3Wei Ding4Division of Nephrology, The Fifth People’s Hospital of Shanghai, Fudan University, 128 Ruili Road, Shanghai 200240, ChinaDivision of Nephrology, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiaotong University, 639 Zhizaoju Road, Shanghai 200011, ChinaDepartment of Pediatrics, The 2nd Hospital of Harbin Medical University, Harbin 150086, ChinaDivision of Nephrology, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiaotong University, 639 Zhizaoju Road, Shanghai 200011, ChinaDivision of Nephrology, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiaotong University, 639 Zhizaoju Road, Shanghai 200011, ChinaBackground and Aims. The nucleotide-binding domain and leucine-rich repeat containing PYD-3 (NLRP3) inflammasome has been implicated in the pathogenesis of chronic kidney disease (CKD); however, its exact role in glomerular injury and tubulointerstitial fibrosis is still undefined. The present study was performed to identify the function of NLRP3 in modulating renal injury and fibrosis and the potential involvement of mitochondrial dysfunction in the murine unilateral ureteral obstruction (UUO) model of CKD. Methods. Employing wild-type (WT) and NLRP3−/− mice with or without UUO, we evaluated renal structure, tissue injury, and mitochondrial ultrastructure, as well as expression of some vital molecules involved in the progression of fibrosis, apoptosis, inflammation, and mitochondrial dysfunction. Results. The severe glomerular injury and tubulointerstitial fibrosis induced in WT mice by UUO was markedly attenuated in NLRP3−/− mice as evidenced by blockade of extracellular matrix deposition, decreased cell apoptosis, and phenotypic alterations. Moreover, NLRP3 deletion reversed UUO-induced impairment of mitochondrial morphology and function. Conclusions. NLRP3 deletion ameliorates mitochondrial dysfunction and alleviates renal fibrosis in a murine UUO model of CKD.http://dx.doi.org/10.1155/2017/8316560 |
| spellingShingle | Honglei Guo Xiao Bi Ping Zhou Shijian Zhu Wei Ding NLRP3 Deficiency Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in a Mouse Unilateral Ureteral Obstruction Model of Chronic Kidney Disease Mediators of Inflammation |
| title | NLRP3 Deficiency Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in a Mouse Unilateral Ureteral Obstruction Model of Chronic Kidney Disease |
| title_full | NLRP3 Deficiency Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in a Mouse Unilateral Ureteral Obstruction Model of Chronic Kidney Disease |
| title_fullStr | NLRP3 Deficiency Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in a Mouse Unilateral Ureteral Obstruction Model of Chronic Kidney Disease |
| title_full_unstemmed | NLRP3 Deficiency Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in a Mouse Unilateral Ureteral Obstruction Model of Chronic Kidney Disease |
| title_short | NLRP3 Deficiency Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in a Mouse Unilateral Ureteral Obstruction Model of Chronic Kidney Disease |
| title_sort | nlrp3 deficiency attenuates renal fibrosis and ameliorates mitochondrial dysfunction in a mouse unilateral ureteral obstruction model of chronic kidney disease |
| url | http://dx.doi.org/10.1155/2017/8316560 |
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