Effects of PI3-k/Akt short hairpin RNA on proliferation, fibronectin production and synthesis of thrombospondin-1 and transforming growth factor-beta1 in glomerular mesangial cells induced by sublytic C5b-9 complexes

Cell Prolif. 2009 Feb;42(1):83-93. doi: 10.1111/j.1365-2184.2008.00575.x.

Abstract

Objectives: To explore proliferation of glomerular mesangial cells (GMC) and secretion of extracellular matrix (fibronectin induced by sublytic C5b-9 complexes), and then ascertain the role of phosphatidylinositol 3-kinase (PI3-k)/Akt signal pathway in these processes, by using small hairpin RNAs.

Material and methods: The expression of cyclin D(2), (3)H-thymidine into DNA and production of fibronectin including thrombospondin-1 and transforming growth factor-beta(1) in the GMCs stimulated by sublytic C5b-9 or transfected with expression vectors of PI3-k and Akt short hairpin RNA or LY294002 (PI3-k inhibitor) were measured by Real-time quantitative polymerase chain reaction (PCR), Western blot, enzyme-linked immunosorbent assay (ELISA) and (3)H-thymidine incorporation ((3)H-TdR), respectively.

Results: The expression of cyclin D(2), (3)H-thymidine into DNA and fibronectin in the GMCs stimulated by sublytic C5b-9 could all be increased, and the elevations of these parameters mentioned above were also markedly reduced in the GMCs transfected with vectors of PI3-k and Akt short hairpin RNA or LY294002, respectively.

Conclusions: These data indicate that sublytic C5b-9 can promote proliferation of GMCs and secretion of fibronectin as well as synthesis of thrombospondin-1 and transforming growth factor-beta(1). The PI3-k/Akt signal pathway in these reactions, mediated by sublytic C5b-9 complexes, may play at least a partial role.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Blotting, Western
  • Cell Proliferation*
  • Complement C5b / metabolism*
  • Complement C9 / metabolism*
  • DNA Primers
  • Enzyme-Linked Immunosorbent Assay
  • Fibronectins / biosynthesis*
  • Glomerular Mesangium / enzymology
  • Glomerular Mesangium / metabolism*
  • Phosphatidylinositol 3-Kinases / genetics*
  • Plasmids
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-akt / genetics*
  • RNA / genetics*
  • Rats
  • Thrombospondin 1 / biosynthesis*
  • Transforming Growth Factor beta1 / biosynthesis*

Substances

  • Complement C9
  • DNA Primers
  • Fibronectins
  • Thrombospondin 1
  • Transforming Growth Factor beta1
  • RNA
  • Complement C5b
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt