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Leptospiral outer membrane protein induces extracellular matrix accumulation through a TGF-beta1/Smad-dependent

Ya-Chung Tian1, Yung-Chang Chen, Cheng-Chieh Hung

  • 1Kidney Institute, Department of Nephrology, Chang Gung Memorial Hospital, 199 Tun-Hwa North Road, Taipei 105, Taiwan.

Journal of the American Society of Nephrology : JASN
|August 25, 2006
PubMed

Insights

Leptospira outer membrane protein (OMP) triggers extracellular matrix accumulation in kidney cells. This process, involving TGF-beta1 and Smad3, contributes to kidney fibrosis and renal failure.

Area of Science:

  • Nephrology
  • Microbiology
  • Cell Biology

Background:

  • Leptospirosis is a significant cause of acute tubulointerstitial nephritis and can lead to renal failure.
  • Untreated leptospira-induced nephritis may result in tubulointerstitial fibrosis, a key factor in chronic kidney disease.

Purpose of the Study:

  • To investigate the effect of Leptospira santarosai serovar Shermani outer membrane protein (OMP) on extracellular matrix (ECM) accumulation in human proximal tubular HK-2 cells.
  • To elucidate the underlying molecular mechanisms, including the role of transforming growth factor-beta1 (TGF-beta1) and the Smad pathway.

Main Methods:

  • HK-2 cells were treated with varying concentrations of Leptospira santarosai serovar Shermani OMP for 72 hours.
  • Collagen production (type I and IV) was quantified using real-time PCR and Western blot analysis.
  • TGF-beta1 secretion and Smad3 signaling pathway activation were assessed, with and without neutralizing antibodies or dominant-negative Smad3.

Main Results:

  • Leptospira santarosai serovar Shermani OMP significantly increased the production of type I and type IV collagens in HK-2 cells in a dose-dependent manner.
  • OMP treatment led to a nearly two-fold increase in active TGF-beta1 secretion.
  • Inhibition of TGF-beta1 or Smad3 signaling pathways attenuated the OMP-induced collagen production.

Conclusions:

  • Leptospira santarosai serovar Shermani OMP directly stimulates extracellular matrix production in renal proximal tubular cells.
  • The OMP-induced ECM accumulation is mediated by the activation of the TGF-beta1/Smad3 signaling pathway.
  • These findings highlight a potential mechanism linking leptospirosis infection to the development of renal fibrosis.

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