Abstract
Backgrounds: Klotho protein interacts with the transforming growth factor β (TGF-β) receptor and Wnt, which contribute to the progression of renal disease, inhibiting their signals. Renal and circulating klotho levels are diminished in chronic kidney disease. Methods: Experiments were performed to assess whether supplementation of klotho protein could have protective effects on the kidney. Rats were injected with adriamycin (5 mg/kg) and divided into three groups: Those treated with vehicle, those treated with klotho protein and those treated with klotho plus 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD). Rats without adriamycin treatment were used as a control. Results: Adriamycin reduced the serum klotho concentration and renal expression of klotho and E-cadherin. Adriamycin also increased the renal expression of Wnt, TGF-β, and angiotensinogen, as well as the renal abundance of b-catenin and angiotensin II. Klotho supplementation suppressed adriamycininduced elevations of b-catenin and angiotensin II with sustained Wnt expression. Combined treatment with klotho and TDZD reversed the klotho-induced improvements in the renal abundance of b-catenin and angiotensin II as well as the expression of TGF-β and angiotensinogen without affecting Ecadherin. Conclusions: Our data indicate that Wnt is involved in the pathogenesis of adriamycin nephropathy. Furthermore, klotho supplementation inhibited Wnt signaling, ameliorating renal angiotensin II. Finally, klotho protein appears to suppress epithelial- mesenchymal transition by inhibiting TGF-β and Wnt signaling.
| Original language | English |
|---|---|
| Pages (from-to) | 791-800 |
| Number of pages | 10 |
| Journal | Nephrology Dialysis Transplantation |
| Volume | 32 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2017 May 1 |
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Keywords
- b-catenin
- fibrosis
- nephrin
- oxidative stress
- TRPC6
ASJC Scopus subject areas
- Nephrology
- Transplantation
Cite this
Klotho suppresses the renin-angiotensin system in adriamycin nephropathy. / Takenaka, Tsuneo; Inoue, Tsutomu; Miyazaki, Takashi; Kobori, Hiroyuki; Nishiyama, Akira; Ishii, Naohito; Hayashi, Matsuhiko; Suzuki, Hiromichi.
In: Nephrology Dialysis Transplantation, Vol. 32, No. 5, 01.05.2017, p. 791-800.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Klotho suppresses the renin-angiotensin system in adriamycin nephropathy
AU - Takenaka, Tsuneo
AU - Inoue, Tsutomu
AU - Miyazaki, Takashi
AU - Kobori, Hiroyuki
AU - Nishiyama, Akira
AU - Ishii, Naohito
AU - Hayashi, Matsuhiko
AU - Suzuki, Hiromichi
PY - 2017/5/1
Y1 - 2017/5/1
N2 - Backgrounds: Klotho protein interacts with the transforming growth factor β (TGF-β) receptor and Wnt, which contribute to the progression of renal disease, inhibiting their signals. Renal and circulating klotho levels are diminished in chronic kidney disease. Methods: Experiments were performed to assess whether supplementation of klotho protein could have protective effects on the kidney. Rats were injected with adriamycin (5 mg/kg) and divided into three groups: Those treated with vehicle, those treated with klotho protein and those treated with klotho plus 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD). Rats without adriamycin treatment were used as a control. Results: Adriamycin reduced the serum klotho concentration and renal expression of klotho and E-cadherin. Adriamycin also increased the renal expression of Wnt, TGF-β, and angiotensinogen, as well as the renal abundance of b-catenin and angiotensin II. Klotho supplementation suppressed adriamycininduced elevations of b-catenin and angiotensin II with sustained Wnt expression. Combined treatment with klotho and TDZD reversed the klotho-induced improvements in the renal abundance of b-catenin and angiotensin II as well as the expression of TGF-β and angiotensinogen without affecting Ecadherin. Conclusions: Our data indicate that Wnt is involved in the pathogenesis of adriamycin nephropathy. Furthermore, klotho supplementation inhibited Wnt signaling, ameliorating renal angiotensin II. Finally, klotho protein appears to suppress epithelial- mesenchymal transition by inhibiting TGF-β and Wnt signaling.
AB - Backgrounds: Klotho protein interacts with the transforming growth factor β (TGF-β) receptor and Wnt, which contribute to the progression of renal disease, inhibiting their signals. Renal and circulating klotho levels are diminished in chronic kidney disease. Methods: Experiments were performed to assess whether supplementation of klotho protein could have protective effects on the kidney. Rats were injected with adriamycin (5 mg/kg) and divided into three groups: Those treated with vehicle, those treated with klotho protein and those treated with klotho plus 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD). Rats without adriamycin treatment were used as a control. Results: Adriamycin reduced the serum klotho concentration and renal expression of klotho and E-cadherin. Adriamycin also increased the renal expression of Wnt, TGF-β, and angiotensinogen, as well as the renal abundance of b-catenin and angiotensin II. Klotho supplementation suppressed adriamycininduced elevations of b-catenin and angiotensin II with sustained Wnt expression. Combined treatment with klotho and TDZD reversed the klotho-induced improvements in the renal abundance of b-catenin and angiotensin II as well as the expression of TGF-β and angiotensinogen without affecting Ecadherin. Conclusions: Our data indicate that Wnt is involved in the pathogenesis of adriamycin nephropathy. Furthermore, klotho supplementation inhibited Wnt signaling, ameliorating renal angiotensin II. Finally, klotho protein appears to suppress epithelial- mesenchymal transition by inhibiting TGF-β and Wnt signaling.
KW - b-catenin
KW - fibrosis
KW - nephrin
KW - oxidative stress
KW - TRPC6
UR - http://www.scopus.com/inward/record.url?scp=85020179134&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85020179134&partnerID=8YFLogxK
U2 - 10.1093/ndt/gfw340
DO - 10.1093/ndt/gfw340
M3 - Article
VL - 32
SP - 791
EP - 800
JO - Nephrology Dialysis Transplantation
JF - Nephrology Dialysis Transplantation
SN - 0931-0509
IS - 5
ER -