Archives of Pharmacal Research

, Volume 33, Issue 2, pp 275–284

LSKL, a peptide antagonist of thrombospondin-1, attenuates renal interstitial fibrosis in rats with unilateral ureteral obstruction

  • Xi-sheng Xie
  • Fei-yan Li
  • Heng-chuan Liu
  • Yao Deng
  • Zi Li
  • Jun-ming Fan
Research Articles Drug Actions

DOI: 10.1007/s12272-010-0213-6

Cite this article as:
Xie, X., Li, F., Liu, H. et al. Arch. Pharm. Res. (2010) 33: 275. doi:10.1007/s12272-010-0213-6

Abstract

The effects of LSKL, the peptide antagonist of thrombospondin-1 (TSP-1), on renal interstitial fibrosis in rats subjected to unilateral ureteral obstruction (UUO) were investigated. Rats were divided randomly into three groups (n = 20 each): UUO group, sham-operation group and UUO plus LSKL treatment group. Collagen deposition was studied using histopathology and reverse transcription polymerase chain reaction analysis (RT-PCR). TSP-1, transforming growth factor beta 1 (TGF-β1), phosphorylated Smad2 (pSsmad2) and α-smooth muscle actin (α-SMA) in the kidney were measured using immunocytochemistry, western blotting analysis, RT-PCR and enzyme-linked immunosorbent assay. Biochemical analyses in the serum and urine were made. Histopathology showed severe tubular dilatation and atrophy, interstitial inflammation and collagen accumulation after surgery and LSKL significantly inhibited interstitial fibrosis including tubular injury as well as collagen deposition. The protein and mRNA levels of TSP-1 increased notably at different time point and significantly decreased in the presence of LSKL. The expression of TGF-β1 and pSmad2 were upregulated in the obstructed kidney and substantially suppressed by LSKL treatment. Myofibroblast accumulation could be alleviated after administration of LSKL. Biochemical parameters did not show differences among the three groups. As TSP-1 is the major activator of TGF-β1, we demonstrate that LSKL can attenuate renal interstitial fibrosis in vivo by preventing TSP-1-mediated TGF-β1 activation.

Key words

LSKLRenal interstitial fibrosisTransforming growth factor-β1Thrombospondin-1Myofibroblast

Copyright information

© The Pharmaceutical Society of Korea and Springer Netherlands 2010

Authors and Affiliations

  • Xi-sheng Xie
    • 1
  • Fei-yan Li
    • 2
  • Heng-chuan Liu
    • 3
  • Yao Deng
    • 1
  • Zi Li
    • 1
  • Jun-ming Fan
    • 1
  1. 1.Department of NephrologyWest China Hospital of Sichuan UniversityWuhou, ChengduChina
  2. 2.Department of Respiratory MedicineThe First Affiliated Hospital of Medical College of Xi’an Jiaotong UniversityXi’anChina
  3. 3.Department of Medicine Technology, West China School of Public HealthSichuan UniversityWuhou, ChengduChina