Hypoxia and high glucose cause exaggerated mesangial cell growth and collagen synthesis: Role of osteopontin

Chhinder P. Sodhi, Sarojini A. Phadke, Daniel Batlle, Atul Sahai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

The effect of hypoxia on the proliferation and collagen synthesis of cultured rat mesangial cells was examined under normal-glucose (NG, 5 mM) and high-glucose (HG, 25 mM)-media conditions. In addition, a role for osteopontin (OPN) in mediating these processes was assessed. Quiescent cultures were exposed to hypoxia (3% O2) and normoxia (18% O2) in a serum-free medium with NG or HG, and cell proliferation, collagen synthesis, and OPN expression were assessed. Cells exposed to hypoxia in NG medium resulted in significant increases in [3H]thymidine incorporation, cell number, and [3H]proline incorporation, respectively. HG incubations also produced significant stimulation of these parameters under normoxic conditions, which were markedly enhanced in cells exposed to hypoxia in HG medium. In addition, hypoxia and HG stimulated the mRNA levels of type IV collagen, and the combination of hypoxia and HG resulted in additive increases in type IV collagen expression. Hypoxia and HG also stimulated OPN mRNA and protein levels in an additive fashion. A neutralizing antibody to OPN or its β3-integrin receptor significantly blocked the effect of hypoxia and HG on proliferation and collagen synthesis. In conclusion, these results demonstrate for the first time that hypoxia in HG medium produces exaggerated mesangial cell growth and type IV collagen synthesis. In addition, OPN appears to play a role in mediating the accelerated mesangial cell growth and collagen synthesis found in a hyperglycemic and hypoxic environment.

Original languageEnglish (US)
Pages (from-to)F667-F674
JournalAmerican Journal of Physiology - Renal Physiology
Volume280
Issue number4 49-4
StatePublished - Apr 1 2001

Keywords

  • Cell proliferation
  • Chronic hypoxia
  • Diabetes
  • Extracellular matrix
  • Hyperglycemia
  • Mesangial cells

ASJC Scopus subject areas

  • Physiology
  • Urology

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