Protective effects of klotho on palmitate-induced podocyte injury in diabetic nephropathy.
The anti-aging gene, klotho, has been identified as a multi-functional humoral factor and is implicated in multiple biological processes. However, the effects of klotho on podocyte injury in diabetic nephropathy are poorly understood. Thus, the current study aims to investigate the renoprotective ef...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0250666 |
| _version_ | 1818364321427619840 |
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| author | Jeong Suk Kang Seung Seob Son Ji-Hye Lee Seong Woo Lee Ah Reum Jeong Eun Soo Lee Seung-Kuy Cha Choon Hee Chung Eun Young Lee |
| author_facet | Jeong Suk Kang Seung Seob Son Ji-Hye Lee Seong Woo Lee Ah Reum Jeong Eun Soo Lee Seung-Kuy Cha Choon Hee Chung Eun Young Lee |
| author_sort | Jeong Suk Kang |
| collection | DOAJ |
| description | The anti-aging gene, klotho, has been identified as a multi-functional humoral factor and is implicated in multiple biological processes. However, the effects of klotho on podocyte injury in diabetic nephropathy are poorly understood. Thus, the current study aims to investigate the renoprotective effects of klotho against podocyte injury in diabetic nephropathy. We examined lipid accumulation and klotho expression in the kidneys of diabetic patients and animals. We stimulated cultured mouse podocytes with palmitate to induce lipotoxicity-mediated podocyte injury with or without recombinant klotho. Klotho level was decreased in podocytes of lipid-accumulated obese diabetic kidneys and palmitate-treated mouse podocytes. Palmitate-treated podocytes showed increased apoptosis, intracellular ROS, ER stress, inflammation, and fibrosis, and these were significantly attenuated by klotho administration. Klotho treatment restored palmitate-induced downregulation of the antioxidant molecules, Nrf2, Keap1, and SOD1. Klotho inhibited the phosphorylation of FOXO3a, promoted its nuclear translocation, and then upregulated MnSOD expression. In addition, klotho administration attenuated palmitate-induced cytoskeleton changes, decreased nephrin expression, and increased TRPC6 expression, eventually improving podocyte albumin permeability. These results suggest that klotho administration prevents palmitate-induced functional and morphological podocyte injuries, and this may indicate that klotho is a potential therapeutic agent for the treatment of podocyte injury in obese diabetic nephropathy. |
| first_indexed | 2024-12-13T22:02:31Z |
| format | Article |
| id | doaj.art-eee64d9859f1441b8eaaed9ea07f676d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T22:02:31Z |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-eee64d9859f1441b8eaaed9ea07f676d2022-12-21T23:29:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01164e025066610.1371/journal.pone.0250666Protective effects of klotho on palmitate-induced podocyte injury in diabetic nephropathy.Jeong Suk KangSeung Seob SonJi-Hye LeeSeong Woo LeeAh Reum JeongEun Soo LeeSeung-Kuy ChaChoon Hee ChungEun Young LeeThe anti-aging gene, klotho, has been identified as a multi-functional humoral factor and is implicated in multiple biological processes. However, the effects of klotho on podocyte injury in diabetic nephropathy are poorly understood. Thus, the current study aims to investigate the renoprotective effects of klotho against podocyte injury in diabetic nephropathy. We examined lipid accumulation and klotho expression in the kidneys of diabetic patients and animals. We stimulated cultured mouse podocytes with palmitate to induce lipotoxicity-mediated podocyte injury with or without recombinant klotho. Klotho level was decreased in podocytes of lipid-accumulated obese diabetic kidneys and palmitate-treated mouse podocytes. Palmitate-treated podocytes showed increased apoptosis, intracellular ROS, ER stress, inflammation, and fibrosis, and these were significantly attenuated by klotho administration. Klotho treatment restored palmitate-induced downregulation of the antioxidant molecules, Nrf2, Keap1, and SOD1. Klotho inhibited the phosphorylation of FOXO3a, promoted its nuclear translocation, and then upregulated MnSOD expression. In addition, klotho administration attenuated palmitate-induced cytoskeleton changes, decreased nephrin expression, and increased TRPC6 expression, eventually improving podocyte albumin permeability. These results suggest that klotho administration prevents palmitate-induced functional and morphological podocyte injuries, and this may indicate that klotho is a potential therapeutic agent for the treatment of podocyte injury in obese diabetic nephropathy.https://doi.org/10.1371/journal.pone.0250666 |
| spellingShingle | Jeong Suk Kang Seung Seob Son Ji-Hye Lee Seong Woo Lee Ah Reum Jeong Eun Soo Lee Seung-Kuy Cha Choon Hee Chung Eun Young Lee Protective effects of klotho on palmitate-induced podocyte injury in diabetic nephropathy. PLoS ONE |
| title | Protective effects of klotho on palmitate-induced podocyte injury in diabetic nephropathy. |
| title_full | Protective effects of klotho on palmitate-induced podocyte injury in diabetic nephropathy. |
| title_fullStr | Protective effects of klotho on palmitate-induced podocyte injury in diabetic nephropathy. |
| title_full_unstemmed | Protective effects of klotho on palmitate-induced podocyte injury in diabetic nephropathy. |
| title_short | Protective effects of klotho on palmitate-induced podocyte injury in diabetic nephropathy. |
| title_sort | protective effects of klotho on palmitate induced podocyte injury in diabetic nephropathy |
| url | https://doi.org/10.1371/journal.pone.0250666 |
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