Activation of TRPV4 by lactate as a critical mediator of renal fibrosis in spontaneously hypertensive rats after moderate- and high-intensity exercise
Moderate-intensity exercise training has been regarded a healthy way to alleviate kidney fibrosis by the transforming growth factor-beta (TGFβ) signaling pathway. However, the impact of different intensity exercise training on renal function is unknown, and the underlying mechanism is also unclear....
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2022.927078/full |
| _version_ | 1811275299843735552 |
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| author | Binyi Zhao Yanping Xu Yunlin Chen Ying Cai Zhiyan Gong Dan Li Hongyu Kuang Xiaozhu Liu Hao Zhou Guochun Liu Yuehui Yin |
| author_facet | Binyi Zhao Yanping Xu Yunlin Chen Ying Cai Zhiyan Gong Dan Li Hongyu Kuang Xiaozhu Liu Hao Zhou Guochun Liu Yuehui Yin |
| author_sort | Binyi Zhao |
| collection | DOAJ |
| description | Moderate-intensity exercise training has been regarded a healthy way to alleviate kidney fibrosis by the transforming growth factor-beta (TGFβ) signaling pathway. However, the impact of different intensity exercise training on renal function is unknown, and the underlying mechanism is also unclear. The purpose of this study is to explore the effect of lactic acid in different intensity exercise training on renal fibrosis in spontaneous hypertension. Masson’s trichrome staining, immunohistochemistry, lactic acid kit, and Western blotting were applied on the excised renal tissue from six male Wistar–Kyoto rats (WKY) and 18 male spontaneously hypertensive rats (SHR), which were randomly divided into a sedentary hypertensive group (SHR), moderate-intensity exercise hypertensive group (SHR-M), and high-intensity exercise hypertensive group (SHR-H). The results revealed that renal and blood lactic acid, as well as the key fibrotic protein levels of transient receptor potential vanilloid 4 (TRPV4), TGFβ-1, phospho-Smad2/3 (p-Smad2/3), and connective tissue growth factor (CTGF), were significantly decreased in the SHR-M group when compared with the SHR and SHR-H groups. In further in vitro experiments, we selected normal rat kidney interstitial fibroblast (NRK-49F) cells. By immunofluorescence and Western blotting techniques, we found that TRPV4 antagonists (RN-1734) markedly inhibited lactate-induced fibrosis. In conclusion, compared with previous studies, high-intensity exercise training (HIET) can cause adverse effects (renal damage and fibrosis). High concentrations of lactic acid can aggravate renal fibrosis conditions via activating TRPV4-TGFβ1-SMAD2/3-CTGF-mediated renal fibrotic pathways in spontaneous hypertension. This finding might provide new ideas for treating hypertensive nephropathy with different intensity exercise in the future. |
| first_indexed | 2024-04-12T23:35:26Z |
| format | Article |
| id | doaj.art-f154b33c1365488b872c190072263182 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-12T23:35:26Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-f154b33c1365488b872c1900722631822022-12-22T03:12:09ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-09-011310.3389/fphys.2022.927078927078Activation of TRPV4 by lactate as a critical mediator of renal fibrosis in spontaneously hypertensive rats after moderate- and high-intensity exerciseBinyi Zhao0Yanping Xu1Yunlin Chen2Ying Cai3Zhiyan Gong4Dan Li5Hongyu Kuang6Xiaozhu Liu7Hao Zhou8Guochun Liu9Yuehui Yin10Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDepartment of Ultrasonography, The First Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaThe College of Exercise Medicine, Chongqing Medical University, Chongqing, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaModerate-intensity exercise training has been regarded a healthy way to alleviate kidney fibrosis by the transforming growth factor-beta (TGFβ) signaling pathway. However, the impact of different intensity exercise training on renal function is unknown, and the underlying mechanism is also unclear. The purpose of this study is to explore the effect of lactic acid in different intensity exercise training on renal fibrosis in spontaneous hypertension. Masson’s trichrome staining, immunohistochemistry, lactic acid kit, and Western blotting were applied on the excised renal tissue from six male Wistar–Kyoto rats (WKY) and 18 male spontaneously hypertensive rats (SHR), which were randomly divided into a sedentary hypertensive group (SHR), moderate-intensity exercise hypertensive group (SHR-M), and high-intensity exercise hypertensive group (SHR-H). The results revealed that renal and blood lactic acid, as well as the key fibrotic protein levels of transient receptor potential vanilloid 4 (TRPV4), TGFβ-1, phospho-Smad2/3 (p-Smad2/3), and connective tissue growth factor (CTGF), were significantly decreased in the SHR-M group when compared with the SHR and SHR-H groups. In further in vitro experiments, we selected normal rat kidney interstitial fibroblast (NRK-49F) cells. By immunofluorescence and Western blotting techniques, we found that TRPV4 antagonists (RN-1734) markedly inhibited lactate-induced fibrosis. In conclusion, compared with previous studies, high-intensity exercise training (HIET) can cause adverse effects (renal damage and fibrosis). High concentrations of lactic acid can aggravate renal fibrosis conditions via activating TRPV4-TGFβ1-SMAD2/3-CTGF-mediated renal fibrotic pathways in spontaneous hypertension. This finding might provide new ideas for treating hypertensive nephropathy with different intensity exercise in the future.https://www.frontiersin.org/articles/10.3389/fphys.2022.927078/fullSHR (spontaneous hypertensive rat)exerciseTRPV4 (transient receptor potential vanilloid 4)lactaterenalfibrosis |
| spellingShingle | Binyi Zhao Yanping Xu Yunlin Chen Ying Cai Zhiyan Gong Dan Li Hongyu Kuang Xiaozhu Liu Hao Zhou Guochun Liu Yuehui Yin Activation of TRPV4 by lactate as a critical mediator of renal fibrosis in spontaneously hypertensive rats after moderate- and high-intensity exercise Frontiers in Physiology SHR (spontaneous hypertensive rat) exercise TRPV4 (transient receptor potential vanilloid 4) lactate renal fibrosis |
| title | Activation of TRPV4 by lactate as a critical mediator of renal fibrosis in spontaneously hypertensive rats after moderate- and high-intensity exercise |
| title_full | Activation of TRPV4 by lactate as a critical mediator of renal fibrosis in spontaneously hypertensive rats after moderate- and high-intensity exercise |
| title_fullStr | Activation of TRPV4 by lactate as a critical mediator of renal fibrosis in spontaneously hypertensive rats after moderate- and high-intensity exercise |
| title_full_unstemmed | Activation of TRPV4 by lactate as a critical mediator of renal fibrosis in spontaneously hypertensive rats after moderate- and high-intensity exercise |
| title_short | Activation of TRPV4 by lactate as a critical mediator of renal fibrosis in spontaneously hypertensive rats after moderate- and high-intensity exercise |
| title_sort | activation of trpv4 by lactate as a critical mediator of renal fibrosis in spontaneously hypertensive rats after moderate and high intensity exercise |
| topic | SHR (spontaneous hypertensive rat) exercise TRPV4 (transient receptor potential vanilloid 4) lactate renal fibrosis |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2022.927078/full |
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