INFLAMMATORY MEDIATORS AND GLOMERULAR CELLS IN CULTURE

Project: Research project

Project Details

Description

Activation of mesangial cells with subsequent focal or diffuse proliferation and expansion of the mesangial cell matrix is a common manifestation of glomerular injury whether primary or secondary to interstitial disease. We have been studying mechanisms of mesangial cell injury in vitro and in-vivo models in rats and mice. Our work and work by others demonstrated that release of inflammatory cytokines is one mechanism by which mesangial cells respond to injury. We plan to study two model systems that represent effector function of mesangial cells. The first system deals with platelet-derived growth factor B- chain molecule regulation in mesangial cells. The second system deals with monocyte chemotactic peptide (MCP-1) whose constitutive expression is very low in mesangial cells yet can be upregulated by immune mediators. Immune-modulatory cytokines including interferon gamma (IFN-gamma), tumor necrosis factor (TNF) and interleukin 1 (IL- 1) induce MCP-1 gene expression and protein secretion. In vitro and in vivo methodology will be used to study these two systems. Expression of PDGF in mesangial cells is regulated at the transcriptional level in response to PDGF itself, thrombin and phorbol esters. For both PDGF-B and MCP-1, we plan to identify specific cis-acting DNA elements which mediate transcriptional regulation. This will be accomplished by use of plasmids in which fragments of the proximal 5'-flanking region of PDGF B-chain or MCP-1 genes have been inserted upstream of a reporter gene, transfection of these plasmids into mesangial cells and studying the regulation of response to PDGF, thrombin, or phorbol esters for PDGF gene and IFN-gamma or IL-1 for MCP-1 gene. We will characterize the protein DNA interactions by gel retardation and DNAse footprint analysis. Our approach will lead to a better understanding of the role of mesangial cells in glomerular injury.
StatusFinished
Effective start/end date12/1/848/31/16

Funding

  • National Institutes of Health
  • National Institutes of Health: $325,163.00
  • National Institutes of Health: $42,050.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $283,392.00
  • National Institutes of Health: $208,764.00
  • National Institutes of Health: $143,604.00
  • National Institutes of Health: $282,189.00
  • National Institutes of Health: $193,565.00
  • National Institutes of Health: $277,854.00
  • National Institutes of Health: $203,545.00
  • National Institutes of Health: $42,050.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $24,210.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $197,613.00
  • National Institutes of Health: $313,783.00
  • National Institutes of Health: $325,163.00
  • National Institutes of Health
  • National Institutes of Health: $149,349.00
  • National Institutes of Health: $42,050.00
  • National Institutes of Health: $289,761.00
  • National Institutes of Health: $279,462.00
  • National Institutes of Health: $86,065.00
  • National Institutes of Health: $325,163.00
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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