Klotho Ameliorates Podocyte Injury through Targeting TRPC6 Channel in Diabetic Nephropathy
Podocyte damage is vital for the etiopathogenesis of diabetic nephropathy (DN). Klotho (KL), a multifunctional protein, has been demonstrated to have renoprotective effects; nevertheless, the mechanism for protective effect has not been completely elucidated. Transient receptor potential cation chan...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2022/1329380 |
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| author | Xingmei Yao Hengjiang Guo Mengyao Sun Sixuan Meng Bingbing Zhu Ji Fang Jiebo Huang Hao Wang Lina Xing |
| author_facet | Xingmei Yao Hengjiang Guo Mengyao Sun Sixuan Meng Bingbing Zhu Ji Fang Jiebo Huang Hao Wang Lina Xing |
| author_sort | Xingmei Yao |
| collection | DOAJ |
| description | Podocyte damage is vital for the etiopathogenesis of diabetic nephropathy (DN). Klotho (KL), a multifunctional protein, has been demonstrated to have renoprotective effects; nevertheless, the mechanism for protective effect has not been completely elucidated. Transient receptor potential cation channel subfamily C, member 6 (TRPC6), a potential target of KL, is implicated in glomerular pathophysiology. Here, we sought to determine whether KL could protect against podocyte injury through inhibiting TRPC6 in DN. We found that high glucose (HG) triggered podocyte injury as manifested by actin cytoskeleton damage along with the downregulation of KL and Synaptopodin and the upregulation of TRPC6. KL overexpression reversed HG-induced podocytes injury, whereas cotreatment with TRPC6 activator flufenamic acid (FFA) significantly abrogated the beneficial effects conferred by KL. Moreover, KL knockdown in podocytes resulted in actin cytoskeleton impairment, decreased Synaptopodin expression, and increased TRPC6 expression. In db/db mice, KL overexpression inhibited TRPC6 expression and attenuated diabetes-induced podocyte injury, which was accompanied by decreased albuminuria and ameliorated glomerulosclerosis. Our data provided novel mechanistic insights for KL against DN and highlighted TRPC6 as a new target for KL in podocytes to prevent DN. |
| format | Article |
| id | doaj-art-2a77152f7a5e476da230db72c01546a8 |
| institution | Kabale University |
| issn | 2314-6753 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-2a77152f7a5e476da230db72c01546a82025-02-03T05:53:40ZengWileyJournal of Diabetes Research2314-67532022-01-01202210.1155/2022/1329380Klotho Ameliorates Podocyte Injury through Targeting TRPC6 Channel in Diabetic NephropathyXingmei Yao0Hengjiang Guo1Mengyao Sun2Sixuan Meng3Bingbing Zhu4Ji Fang5Jiebo Huang6Hao Wang7Lina Xing8Department of NephrologyDepartment of AnesthesiologyDepartment of NephrologyDepartment of NephrologyDepartment of NephrologyDepartment of NephrologyDepartment of NephrologyDepartment of NephrologyDepartment of NephrologyPodocyte damage is vital for the etiopathogenesis of diabetic nephropathy (DN). Klotho (KL), a multifunctional protein, has been demonstrated to have renoprotective effects; nevertheless, the mechanism for protective effect has not been completely elucidated. Transient receptor potential cation channel subfamily C, member 6 (TRPC6), a potential target of KL, is implicated in glomerular pathophysiology. Here, we sought to determine whether KL could protect against podocyte injury through inhibiting TRPC6 in DN. We found that high glucose (HG) triggered podocyte injury as manifested by actin cytoskeleton damage along with the downregulation of KL and Synaptopodin and the upregulation of TRPC6. KL overexpression reversed HG-induced podocytes injury, whereas cotreatment with TRPC6 activator flufenamic acid (FFA) significantly abrogated the beneficial effects conferred by KL. Moreover, KL knockdown in podocytes resulted in actin cytoskeleton impairment, decreased Synaptopodin expression, and increased TRPC6 expression. In db/db mice, KL overexpression inhibited TRPC6 expression and attenuated diabetes-induced podocyte injury, which was accompanied by decreased albuminuria and ameliorated glomerulosclerosis. Our data provided novel mechanistic insights for KL against DN and highlighted TRPC6 as a new target for KL in podocytes to prevent DN.http://dx.doi.org/10.1155/2022/1329380 |
| spellingShingle | Xingmei Yao Hengjiang Guo Mengyao Sun Sixuan Meng Bingbing Zhu Ji Fang Jiebo Huang Hao Wang Lina Xing Klotho Ameliorates Podocyte Injury through Targeting TRPC6 Channel in Diabetic Nephropathy Journal of Diabetes Research |
| title | Klotho Ameliorates Podocyte Injury through Targeting TRPC6 Channel in Diabetic Nephropathy |
| title_full | Klotho Ameliorates Podocyte Injury through Targeting TRPC6 Channel in Diabetic Nephropathy |
| title_fullStr | Klotho Ameliorates Podocyte Injury through Targeting TRPC6 Channel in Diabetic Nephropathy |
| title_full_unstemmed | Klotho Ameliorates Podocyte Injury through Targeting TRPC6 Channel in Diabetic Nephropathy |
| title_short | Klotho Ameliorates Podocyte Injury through Targeting TRPC6 Channel in Diabetic Nephropathy |
| title_sort | klotho ameliorates podocyte injury through targeting trpc6 channel in diabetic nephropathy |
| url | http://dx.doi.org/10.1155/2022/1329380 |
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