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Abstract: SA-PO818

Calcitriol Ameliorates Kidney Injury and Fibrosis by Activating Klotho and Inhibition of TGFβ1 Signaling Pathway

Session Information

Category: CKD (Non-Dialysis)

  • 1903 CKD (Non-Dialysis): Mechanisms

Author

  • Cheng, Ao, The Fist Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
Background

Active vitamin D3 (Calcitriol) can effectively remit the progression of chronic kidney disease, but its mechanism is not clear. Klotho as an anti-aging protein played a variety of physiologic roles in the kidney. The main purpose of this experiment is to explore whether Calcitriol could up-regulated expression of the Klotho in vitro and in vivo, and ameliorates kidney injury and fibrosis by targeted inhibition of TGFβ1 activation.

Methods

(1) Animal Experiment: The rats were divided into three groups: sham group, 5/6 nephrectomy group, 5/6 nephrectomy + calcitriol group. 1) Through serum biochemical tests, to detect the levels of BUN, Creatine in various groups and determine expression of Klotho, TGFβ1 in serum. 2) By HE, Masson staining of renal tussues, Observation of renal fibrosis and collagen deposition; 3) Detection expression of Klotho, TGFβ1, E-cadherin and α-SMA in renal tussues by Immunohistochemical staining. 4) Using PCR and Western-Bloting detect expression of Klotho, TGFβ1, E-cadherin and α-SMA in renal tussues; (2) In Vitro: Calcitriol, Klotho siRNA and TGFβ1 ware prepared and mouse renal tubular epithelial cells were cultured in vitro. Mouse renal tubular epithelial cells was treatment with various concentrations and time period of Calcitriol before TGFβ1 stimulation, and pretreatment or not with Klotho siRNA. Klotho, Snail1, PAI-1, E-cadherin and α-SMA were measured by real-time PCR and Western-blot.

Results

(1) Animal Experiment: 1) Calcitriol could effectively reduce the elevated creatinine, BUN in the 5/6 nephrectomy rats; 2) Calcitriol might ameliorate kidney injury and fibrosis by light microscopy; 3) In renal tissue, calcitriol may induce Klotho and E-cadherin expression and reduce TGFβ1 and α-SMA expression;(2) In Vitrio: Calcitriol in a dose and time dependent manner induce Klotho and E-cadherin expression and reduce Snail1, PAI-1 α-SMA expression by TGFβ1 stimulation. Klotho siRNA could mitigate effective role of Calcitriol.

Conclusion

Calcitriol could ameliorate kidney injury and mitigate TGFβ1 induced fibrosis by activating Klotho in vivo and in vitro.

Funding

  • Government Support - Non-U.S.