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Article

Lefty1 alleviates renal tubulointerstitial injury in mice with unilateral ureteral obstruction

  • Authors:
    • Changgeng Xu
    • Mingwei Xu
    • Wei Wang
    • Jie Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Wuhan Central Hospital, Wuhan, Hubei 430014, P.R. China, Department of Urology, Xiangyang Central Hospital, Xiangyang, Hubei 441021, P.R. China, Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
  • Pages: 901-908
    |
    Published online on: November 30, 2015
       https://doi.org/10.3892/mmr.2015.4631
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Abstract

Lefty is a member of the transforming growth factor (TGF) β superfamily, which is implicated in left‑right patterning during embryogenesis. Previous studies revealed that lefty attenuates the epithelial‑mesenchymal transition in tubular epithelial cells. In the present study, the protective effect of lefty1 on renal interstitial injury was further assessed. Mice with a unilateral ureteral obstruction (UUO) were sacrificed on days 3, 5 and 7 following surgery, and the association between the expression of lefty1 and the degree of interstitial fibrosis was investigated. Subsequently, mice with a UUO were administered recombinant lefty1 (300 µg/kg body weight) or vehicle (0.9% saline solution; 100 µl) through tail‑vein injection every other day for 6 days. The effects of lefty1 were assessed by measuring the degree of tubulointerstitial fibrosis, tubular injury and atrophy, and also by monitoring the expression levels of α‑smooth muscle actin (α‑SMA), TGF‑β1, phosphorylated (p)‑Smad2/3, kidney injury molecular‑1 and endogenous lefty1. The expression of lefty1 in the kidney decreased in a time‑dependent manner in mice with a UUO, which was inversely correlated with the degree of renal interstitial fibrosis. Furthermore, compared with vehicle treatment, lefty1 attenuated renal interstitial fibrosis. Ureteral ligation induced increased expression levels of α‑SMA, TGF‑β1 and p‑Smad2/3. However, these effects were reduced following treatment with lefty1. The UUO also induced tubular injury and atrophy, whereas lefty1 treatment exerted a marked suppressive effect on tubular injury. In addition, exogenous lefty1 administered to mice restored the endogenous expression levels of lefty1. The present study demonstrated that lefty1 attenuated renal interstitial injury by inhibiting the Smad‑dependent TGF‑β1 signaling pathway. Lefty1 may therefore by a putative therapeutic agent in the treatment of renal injury.
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Copy and paste a formatted citation
Spandidos Publications style
Xu C, Xu M, Wang W and Zhang J: Lefty1 alleviates renal tubulointerstitial injury in mice with unilateral ureteral obstruction. Mol Med Rep 13: 901-908, 2016.
APA
Xu, C., Xu, M., Wang, W., & Zhang, J. (2016). Lefty1 alleviates renal tubulointerstitial injury in mice with unilateral ureteral obstruction. Molecular Medicine Reports, 13, 901-908. https://doi.org/10.3892/mmr.2015.4631
MLA
Xu, C., Xu, M., Wang, W., Zhang, J."Lefty1 alleviates renal tubulointerstitial injury in mice with unilateral ureteral obstruction". Molecular Medicine Reports 13.1 (2016): 901-908.
Chicago
Xu, C., Xu, M., Wang, W., Zhang, J."Lefty1 alleviates renal tubulointerstitial injury in mice with unilateral ureteral obstruction". Molecular Medicine Reports 13, no. 1 (2016): 901-908. https://doi.org/10.3892/mmr.2015.4631
Copy and paste a formatted citation
x
Spandidos Publications style
Xu C, Xu M, Wang W and Zhang J: Lefty1 alleviates renal tubulointerstitial injury in mice with unilateral ureteral obstruction. Mol Med Rep 13: 901-908, 2016.
APA
Xu, C., Xu, M., Wang, W., & Zhang, J. (2016). Lefty1 alleviates renal tubulointerstitial injury in mice with unilateral ureteral obstruction. Molecular Medicine Reports, 13, 901-908. https://doi.org/10.3892/mmr.2015.4631
MLA
Xu, C., Xu, M., Wang, W., Zhang, J."Lefty1 alleviates renal tubulointerstitial injury in mice with unilateral ureteral obstruction". Molecular Medicine Reports 13.1 (2016): 901-908.
Chicago
Xu, C., Xu, M., Wang, W., Zhang, J."Lefty1 alleviates renal tubulointerstitial injury in mice with unilateral ureteral obstruction". Molecular Medicine Reports 13, no. 1 (2016): 901-908. https://doi.org/10.3892/mmr.2015.4631
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