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Related Experiment Videos

Human glomeruli express TIMP-1 mRNA and TIMP-2 protein and mRNA

M A Carome1, L J Striker, E P Peten

  • 1Renal Cell Biology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.

The American Journal of Physiology
|June 1, 1993
PubMed
Summary

Glomerulosclerosis involves extracellular matrix imbalance. This study found increased gene expression of tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 in glomeruli affected by sclerosis.

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Area of Science:

  • Nephrology
  • Molecular Biology
  • Pathology

Background:

  • Glomerulosclerosis arises from extracellular matrix imbalances.
  • Metalloproteinases and their inhibitors regulate glomerular matrix degradation.

Purpose of the Study:

  • To investigate the gene expression of tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 in human glomeruli.
  • To examine TIMP-2 protein localization in kidney tissue sections.

Main Methods:

  • Microdissection of glomeruli from human kidney tissue.
  • Reverse transcription and competitive polymerase chain reaction (PCR) assays for TIMP cDNAs.
  • Immunohistochemical detection of TIMP-2 protein.

Main Results:

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  • TIMP-1 and TIMP-2 gene expression was detected in normal human glomeruli.
  • A fourfold increase in TIMP-1 and threefold increase in TIMP-2 cDNA levels was observed in glomerulosclerosis.
  • Elevated TIMP levels were not due to an increased number of glomerular cells.
  • TIMP-2 protein was present in both normal and sclerotic glomeruli.

    • Conclusions:

    • Both TIMP-1 and TIMP-2 genes are expressed in normal glomeruli.
    • Increased TIMP gene expression correlates with glomerulosclerosis, particularly in cases associated with renal carcinoma.
    • TIMP expression may play a role in the development of glomerulosclerosis.