NADPH Oxidase-Induced NALP3 Inflammasome Activation Is Driven by Thioredoxin-Interacting Protein Which Contributes to Podocyte Injury in Hyperglycemia
Diabetic nephropathy (DN) is one of the major causes of end-stage renal disease, and previously we demonstrated that NALP3 inflammasome was involved in the pathogenesis of DN. Here we investigated the mechanisms of NALP3 inflammasome activation in podocyte injury during DN. We found that, besides th...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2015-01-01
|
| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2015/504761 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850159721098510336 |
|---|---|
| author | Pan Gao Fang-Fang He Hui Tang Chun-Tao Lei Shan Chen Xian-Fang Meng Hua Su Chun Zhang |
| author_facet | Pan Gao Fang-Fang He Hui Tang Chun-Tao Lei Shan Chen Xian-Fang Meng Hua Su Chun Zhang |
| author_sort | Pan Gao |
| collection | DOAJ |
| description | Diabetic nephropathy (DN) is one of the major causes of end-stage renal disease, and previously we demonstrated that NALP3 inflammasome was involved in the pathogenesis of DN. Here we investigated the mechanisms of NALP3 inflammasome activation in podocyte injury during DN. We found that, besides the activation of NALP3 inflammasome and upregulated thioredoxin-interacting protein (TXNIP), the glomerular expression of gp91phox, a subunit of NADPH oxidase, was enhanced in DN mice simultaneously. Inhibiting NADPH oxidase abrogated NALP3 inflammasome activation, and IL-1β production and eventually protected podocytes from high glucose- (HG-) induced injury. TXNIP, an inhibitor of thioredoxin, acts as a suppressor for antioxidant defense system. Our observation indicated that in HG-exposed podocytes genetic deletion of TXNIP by shRNA reversed gp91phox overexpression and alleviated the injury of podocyte. Collectively, our findings proposed that HG-induced NADPH oxidase activation was driven by TXNIP which subsequently triggered NALP3 inflammasome activation in podocytes and ultimately led to podocyte injury, and blocking TXNIP/NADPH oxidase signaling may be a promising treatment for DN. |
| format | Article |
| id | doaj-art-b2fdb90b42b34dcfa24a7b5018a00ecb |
| institution | OA Journals |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-b2fdb90b42b34dcfa24a7b5018a00ecb2025-08-20T02:23:25ZengWileyJournal of Diabetes Research2314-67452314-67532015-01-01201510.1155/2015/504761504761NADPH Oxidase-Induced NALP3 Inflammasome Activation Is Driven by Thioredoxin-Interacting Protein Which Contributes to Podocyte Injury in HyperglycemiaPan Gao0Fang-Fang He1Hui Tang2Chun-Tao Lei3Shan Chen4Xian-Fang Meng5Hua Su6Chun Zhang7Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDiabetic nephropathy (DN) is one of the major causes of end-stage renal disease, and previously we demonstrated that NALP3 inflammasome was involved in the pathogenesis of DN. Here we investigated the mechanisms of NALP3 inflammasome activation in podocyte injury during DN. We found that, besides the activation of NALP3 inflammasome and upregulated thioredoxin-interacting protein (TXNIP), the glomerular expression of gp91phox, a subunit of NADPH oxidase, was enhanced in DN mice simultaneously. Inhibiting NADPH oxidase abrogated NALP3 inflammasome activation, and IL-1β production and eventually protected podocytes from high glucose- (HG-) induced injury. TXNIP, an inhibitor of thioredoxin, acts as a suppressor for antioxidant defense system. Our observation indicated that in HG-exposed podocytes genetic deletion of TXNIP by shRNA reversed gp91phox overexpression and alleviated the injury of podocyte. Collectively, our findings proposed that HG-induced NADPH oxidase activation was driven by TXNIP which subsequently triggered NALP3 inflammasome activation in podocytes and ultimately led to podocyte injury, and blocking TXNIP/NADPH oxidase signaling may be a promising treatment for DN.http://dx.doi.org/10.1155/2015/504761 |
| spellingShingle | Pan Gao Fang-Fang He Hui Tang Chun-Tao Lei Shan Chen Xian-Fang Meng Hua Su Chun Zhang NADPH Oxidase-Induced NALP3 Inflammasome Activation Is Driven by Thioredoxin-Interacting Protein Which Contributes to Podocyte Injury in Hyperglycemia Journal of Diabetes Research |
| title | NADPH Oxidase-Induced NALP3 Inflammasome Activation Is Driven by Thioredoxin-Interacting Protein Which Contributes to Podocyte Injury in Hyperglycemia |
| title_full | NADPH Oxidase-Induced NALP3 Inflammasome Activation Is Driven by Thioredoxin-Interacting Protein Which Contributes to Podocyte Injury in Hyperglycemia |
| title_fullStr | NADPH Oxidase-Induced NALP3 Inflammasome Activation Is Driven by Thioredoxin-Interacting Protein Which Contributes to Podocyte Injury in Hyperglycemia |
| title_full_unstemmed | NADPH Oxidase-Induced NALP3 Inflammasome Activation Is Driven by Thioredoxin-Interacting Protein Which Contributes to Podocyte Injury in Hyperglycemia |
| title_short | NADPH Oxidase-Induced NALP3 Inflammasome Activation Is Driven by Thioredoxin-Interacting Protein Which Contributes to Podocyte Injury in Hyperglycemia |
| title_sort | nadph oxidase induced nalp3 inflammasome activation is driven by thioredoxin interacting protein which contributes to podocyte injury in hyperglycemia |
| url | http://dx.doi.org/10.1155/2015/504761 |
| work_keys_str_mv | AT pangao nadphoxidaseinducednalp3inflammasomeactivationisdrivenbythioredoxininteractingproteinwhichcontributestopodocyteinjuryinhyperglycemia AT fangfanghe nadphoxidaseinducednalp3inflammasomeactivationisdrivenbythioredoxininteractingproteinwhichcontributestopodocyteinjuryinhyperglycemia AT huitang nadphoxidaseinducednalp3inflammasomeactivationisdrivenbythioredoxininteractingproteinwhichcontributestopodocyteinjuryinhyperglycemia AT chuntaolei nadphoxidaseinducednalp3inflammasomeactivationisdrivenbythioredoxininteractingproteinwhichcontributestopodocyteinjuryinhyperglycemia AT shanchen nadphoxidaseinducednalp3inflammasomeactivationisdrivenbythioredoxininteractingproteinwhichcontributestopodocyteinjuryinhyperglycemia AT xianfangmeng nadphoxidaseinducednalp3inflammasomeactivationisdrivenbythioredoxininteractingproteinwhichcontributestopodocyteinjuryinhyperglycemia AT huasu nadphoxidaseinducednalp3inflammasomeactivationisdrivenbythioredoxininteractingproteinwhichcontributestopodocyteinjuryinhyperglycemia AT chunzhang nadphoxidaseinducednalp3inflammasomeactivationisdrivenbythioredoxininteractingproteinwhichcontributestopodocyteinjuryinhyperglycemia |