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TBX3, a downstream target of TGF-β1, inhibits mesangial cell apoptosis

Lislaine A Wensing1, Alexandre H Campos2

  • 1Hospital Israelita Albert Einstein, Av. Albert Einstein, 627, Morumbi, 2SS/Bloco A., São Paulo, São Paulo CEP 05651-901, Brazil; Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.

Experimental Cell Research
|August 27, 2014
PubMed

Insights

The study reveals that TBX3, regulated by TGF-β1, protects kidney mesangial cells from apoptosis. Increased TBX3 expression in a kidney disease model suggests its role in preventing glomerulosclerosis and fibrosis.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • Chronic kidney disease (CKD) is a growing global health concern.
  • Mesangial cell (MC) alterations driven by TGF-β1 are implicated in CKD pathogenesis.
  • The role of TBX3 isoforms in kidney disease is not fully understood.

Purpose of the Study:

  • To investigate the role of TBX3 gene expression in TGF-β1-induced mesangial cell alterations.
  • To determine the functional significance of TBX3 in mesangial cell apoptosis.
  • To examine TBX3 protein expression in a preclinical model of kidney injury.

Main Methods:

  • Investigated TGF-β1 regulation of TBX3 gene expression in mesangial cells.
  • Utilized overexpression studies to assess TBX3's effect on serum deprivation-induced apoptosis.
  • Analyzed TBX3 protein levels in glomerular and tubular compartments of a 5/6 nephrectomy rat model.

Main Results:

  • TGF-β1 was found to regulate TBX3 gene expression in mesangial cells.
  • TBX3 overexpression significantly inhibited mesangial cell apoptosis.
  • Elevated TBX3 protein levels correlated with increased TGF-β1, type IV collagen, and fibronectin in a kidney injury model.

Conclusions:

  • TBX3 functions as an anti-apoptotic factor in kidney mesangial cells.
  • TBX3 may mediate TGF-β1-induced glomerulosclerosis and tubular fibrosis in progressive nephropathies.
Keywords:
ApoptosisMesangial cellsTBX3TGF-β1

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