Klotho supplementation reverses renal dysfunction and interstitial fibrosis in remnant kidney.
Introduction: While recent investigations show that klotho exerts reno-protective actions, it has not been fully addressed whether klotho protein supplementation reverses renal damage. Methods: The impacts of subcutaneous klotho supplementation on rats with subtotal nephrectomy were examined. Anima...
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| Format: | Article |
| Language: | English |
| Published: |
Karger Publishers
2023-04-01
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| Series: | Kidney & Blood Pressure Research |
| Online Access: | https://www.karger.com/Article/FullText/530469 |
| _version_ | 1827949304083382272 |
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| author | Tsuneo Takenaka Arif Hasan Takeshi Marumo Tsutomu Inoue Takashi Miyazaki Hiromichi Suzuki Yoshifumi Kurosaki Naohito Ishii Akira Nishiyama Matsuhiko Hayashi |
| author_facet | Tsuneo Takenaka Arif Hasan Takeshi Marumo Tsutomu Inoue Takashi Miyazaki Hiromichi Suzuki Yoshifumi Kurosaki Naohito Ishii Akira Nishiyama Matsuhiko Hayashi |
| author_sort | Tsuneo Takenaka |
| collection | DOAJ |
| description | Introduction: While recent investigations show that klotho exerts reno-protective actions, it has not been fully addressed whether klotho protein supplementation reverses renal damage.
Methods: The impacts of subcutaneous klotho supplementation on rats with subtotal nephrectomy were examined. Animals were divided into 3 groups: group1 (short remnant, SR): remnant kidney for 4 weeks, group 2 (long remnant, LR): remnant kidney for 12 weeks and group 3 (klotho supplementation: KL): klotho protein (20 μg/kg/day) supplementation on the remnant kidney. Blood pressure, blood and urine compositions with conventional methods such as enzyme-linked immunosorbent assay and radioimmunoassay, kidney histology and renal expressions of various genes were analyzed. In vitro studies were also performed to support in vivo findings.
Results: Klotho protein supplementation decreased albuminuria (-43%), systolic blood pressure (-16%), fibroblast growth factor (FGF) 23 (-51%) and serum phosphate levels (-19%), renal angiotensin II concentration (-43%), fibrosis index (-70%), renal expressions of collagen I (-55%) and transforming growth factor β (-59%) (p<0.05 for all). Klotho supplementation enhanced fractional excretion of phosphate (+45%), glomerular filtration rate (+76%), renal expressions of klotho (+148%), superoxide dismutase (+124%) and bone morphogenetic protein (BMP) 7 (+174%) (p<0.05 for all).
Conclusion: Our data indicated that klotho protein supplementation inactivated renal renin-angiotensin system, reducing blood pressure and albuminuria in remnant kidney. Furthermore, exogenous klotho protein supplementation elevated endogenous klotho expression to increase phosphate excretion with resultant reductions in FGF23 and serum phosphate. Finally, klotho supplementation reversed renal dysfunction and fibrosis in association with improved BMP7 in remnant kidney. |
| first_indexed | 2024-04-09T13:08:21Z |
| format | Article |
| id | doaj.art-bb794bd802e6476990d5baa2e0a9c81e |
| institution | Directory Open Access Journal |
| issn | 1420-4096 1423-0143 |
| language | English |
| last_indexed | 2024-04-09T13:08:21Z |
| publishDate | 2023-04-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Kidney & Blood Pressure Research |
| spelling | doaj.art-bb794bd802e6476990d5baa2e0a9c81e2023-05-12T12:24:17ZengKarger PublishersKidney & Blood Pressure Research1420-40961423-01432023-04-011110.1159/000530469530469Klotho supplementation reverses renal dysfunction and interstitial fibrosis in remnant kidney.Tsuneo Takenakahttps://orcid.org/0000-0002-3383-1340Arif HasanTakeshi MarumoTsutomu InoueTakashi MiyazakiHiromichi SuzukiYoshifumi KurosakiNaohito Ishiihttps://orcid.org/0000-0002-1613-1887Akira Nishiyamahttps://orcid.org/0000-0001-5971-820XMatsuhiko HayashiIntroduction: While recent investigations show that klotho exerts reno-protective actions, it has not been fully addressed whether klotho protein supplementation reverses renal damage. Methods: The impacts of subcutaneous klotho supplementation on rats with subtotal nephrectomy were examined. Animals were divided into 3 groups: group1 (short remnant, SR): remnant kidney for 4 weeks, group 2 (long remnant, LR): remnant kidney for 12 weeks and group 3 (klotho supplementation: KL): klotho protein (20 μg/kg/day) supplementation on the remnant kidney. Blood pressure, blood and urine compositions with conventional methods such as enzyme-linked immunosorbent assay and radioimmunoassay, kidney histology and renal expressions of various genes were analyzed. In vitro studies were also performed to support in vivo findings. Results: Klotho protein supplementation decreased albuminuria (-43%), systolic blood pressure (-16%), fibroblast growth factor (FGF) 23 (-51%) and serum phosphate levels (-19%), renal angiotensin II concentration (-43%), fibrosis index (-70%), renal expressions of collagen I (-55%) and transforming growth factor β (-59%) (p<0.05 for all). Klotho supplementation enhanced fractional excretion of phosphate (+45%), glomerular filtration rate (+76%), renal expressions of klotho (+148%), superoxide dismutase (+124%) and bone morphogenetic protein (BMP) 7 (+174%) (p<0.05 for all). Conclusion: Our data indicated that klotho protein supplementation inactivated renal renin-angiotensin system, reducing blood pressure and albuminuria in remnant kidney. Furthermore, exogenous klotho protein supplementation elevated endogenous klotho expression to increase phosphate excretion with resultant reductions in FGF23 and serum phosphate. Finally, klotho supplementation reversed renal dysfunction and fibrosis in association with improved BMP7 in remnant kidney.https://www.karger.com/Article/FullText/530469 |
| spellingShingle | Tsuneo Takenaka Arif Hasan Takeshi Marumo Tsutomu Inoue Takashi Miyazaki Hiromichi Suzuki Yoshifumi Kurosaki Naohito Ishii Akira Nishiyama Matsuhiko Hayashi Klotho supplementation reverses renal dysfunction and interstitial fibrosis in remnant kidney. Kidney & Blood Pressure Research |
| title | Klotho supplementation reverses renal dysfunction and interstitial fibrosis in remnant kidney. |
| title_full | Klotho supplementation reverses renal dysfunction and interstitial fibrosis in remnant kidney. |
| title_fullStr | Klotho supplementation reverses renal dysfunction and interstitial fibrosis in remnant kidney. |
| title_full_unstemmed | Klotho supplementation reverses renal dysfunction and interstitial fibrosis in remnant kidney. |
| title_short | Klotho supplementation reverses renal dysfunction and interstitial fibrosis in remnant kidney. |
| title_sort | klotho supplementation reverses renal dysfunction and interstitial fibrosis in remnant kidney |
| url | https://www.karger.com/Article/FullText/530469 |
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