Min Zhao1,2, Mi Bai1,2,3, Guixia Ding1,2, Yue Zhang1,2, Songming Huang1,2, Zhanjun Jia1,2,3, Aihua Zhang1,2,3. 1. Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing, China. 2. Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China. 3. Nanjing Key Laboratory of Pediatrics, Nanjing, China.
Abstract
BACKGROUND: We previously reported that the NLRP3 inflammasome played an important role in mediating the podocyte injury induced by aldosterone. However, more studies on the role of the NLRP3 inflammasome in the pathogenesis of podocytopathy are still required. The present study was undertaken to study the role of the NLRP3 inflammasome in angiotensin II (Ang II)-induced podocyte injury, as well as the potential mechanisms. METHODS: In this study, we used an Ang II infusion model in NLRP3-/- mice. In cultured podocytes, we used siRNA to silence NLRP3; then we treated the podocytes with Ang II. RESULTS: Following Ang II treatment, we found that the NLRP3 inflammasome was significantly activated in line with mitochondrial dysfunction in a dose- and time-dependent manner. Silencing NLRP3 by siRNA transfection ameliorated podocyte apoptosis, attenuated the loss of the podocyte proteins nephrin and podocin, and protected mitochondrial function. Ang II infusion activated the NLRP3 inflammasome, caused albuminuria, and induced podocyte damage, which was all blocked in the NLRP3-/- mice. At the same time, NLRP3 deletion also ameliorated the mitochondrial dysfunction induced by Ang II infusion. However, the deletion of NLRP3 did not affect the Ang II hypertension. CONCLUSION: Taken together, these results demonstrate an important role of the NLRP3 inflammasome in mediating Ang II-induced podocyte injury and mitochondrial dysfunction, suggesting that the NLRP3 inflammasome might be an effective therapeutic target against podocytopathy.
BACKGROUND: We previously reported that the NLRP3 inflammasome played an important role in mediating the podocyte injury induced by aldosterone. However, more studies on the role of the NLRP3 inflammasome in the pathogenesis of podocytopathy are still required. The present study was undertaken to study the role of the NLRP3 inflammasome in angiotensin II (Ang II)-induced podocyte injury, as well as the potential mechanisms. METHODS: In this study, we used an Ang II infusion model in NLRP3-/- mice. In cultured podocytes, we used siRNA to silence NLRP3; then we treated the podocytes with Ang II. RESULTS: Following Ang II treatment, we found that the NLRP3 inflammasome was significantly activated in line with mitochondrial dysfunction in a dose- and time-dependent manner. Silencing NLRP3 by siRNA transfection ameliorated podocyte apoptosis, attenuated the loss of the podocyte proteins nephrin and podocin, and protected mitochondrial function. Ang II infusion activated the NLRP3 inflammasome, caused albuminuria, and induced podocyte damage, which was all blocked in the NLRP3-/- mice. At the same time, NLRP3 deletion also ameliorated the mitochondrial dysfunction induced by Ang II infusion. However, the deletion of NLRP3 did not affect the Ang II hypertension. CONCLUSION: Taken together, these results demonstrate an important role of the NLRP3 inflammasome in mediating Ang II-induced podocyte injury and mitochondrial dysfunction, suggesting that the NLRP3 inflammasome might be an effective therapeutic target against podocytopathy.
Authors: Akosua Vilaysane; Justin Chun; Mark E Seamone; Wenjie Wang; Rick Chin; Simon Hirota; Yan Li; Sharon A Clark; Jurg Tschopp; Kiril Trpkov; Brenda R Hemmelgarn; Paul L Beck; Daniel A Muruve Journal: J Am Soc Nephrol Date: 2010-08-05 Impact factor: 10.121
Authors: Meena S Madhur; Fernando Elijovich; Matthew R Alexander; Ashley Pitzer; Jeanne Ishimwe; Justin P Van Beusecum; David M Patrick; Charles D Smart; Thomas R Kleyman; Justin Kingery; Robert N Peck; Cheryl L Laffer; Annet Kirabo Journal: Circ Res Date: 2021-04-01 Impact factor: 17.367
Authors: Kathy K Griendling; Livia L Camargo; Francisco J Rios; Rhéure Alves-Lopes; Augusto C Montezano; Rhian M Touyz Journal: Circ Res Date: 2021-04-01 Impact factor: 17.367
Authors: José Wilson N Corrêa; Karoline R Boaro; Letícia B Sene; Juliano Z Polidoro; Thiago A Salles; Flavia L Martins; Lusiane M Bendhack; Adriana C C Girardi Journal: Front Physiol Date: 2021-06-09 Impact factor: 4.566
Authors: Adonis Sfera; Carolina Osorio; Nyla Jafri; Eddie Lee Diaz; Jose E Campo Maldonado Journal: Front Immunol Date: 2020-06-19 Impact factor: 7.561