Growth factor and cytokine modulation of trabecular meshwork matrix metalloproteinase and TIMP expression

J. Preston Alexander, John R. Samples, Ted Acott

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Purpose. We hypothesize that regulated trabecular extracellular matrix (ECM) turnover, initiated by the matrix metalloproteinases, is critical for the maintenance of normal aqueous humor outflow rates. However, very little is known about the regulation of trabecular ECM turnover. To identify candidate trabecular regulators, we evaluated the effects of several growth factors and cytokines on trabecular matrix metalloproteinase and TIMP expression. Methods. Porcine trabecular meshwork cells were treated with several doses of a variety of growth factors and cytokines and culture media was analyzed after 24, 48 and 72 h. Zymograms were used to evaluate stromelysin, gelatinase A and B activity levels, while immunoblots of Western transfers were used to evaluate stromelysin, collagenase, TIMP-1 and TIMP-2 protein levels. Results. A phorbol mitogen (TPA), TNFα and β, interleukin-1α and PDGF BB stimulate gelatinase B, stromelysin, interstitial collagenase and TIMP-1 expression, while having negligible effects on gelatinase A expression; TIMP-2 levels are reduced by TNF but not affected by the other treatments. Acidic and basic FGF, IL-1β, TGFβ and PDGF AB produce similar but smaller effects, while HGF, VEGF, EGF, KGF and LIF produce small to moderate elevations in stromelysin with minimal other responses. PDGF AA, γINF, oncostatin-M and endothelin-1 produce negligible changes in these proteinases and inhibitors. Conclusions. In addition to providing potential ways to modulate trabecular metalloproteinase and TIMP levels, the responsiveness of these cells to some of these growth factors and cytokines suggests possible roles in normal or pathogenic trabecular cell regulation and some may affect aqueous humor outflow.

Original languageEnglish (US)
Pages (from-to)276-285
Number of pages10
JournalCurrent Eye Research
Volume17
Issue number3
DOIs
StatePublished - 1998

Fingerprint

Trabecular Meshwork
Matrix Metalloproteinase 3
Matrix Metalloproteinases
Intercellular Signaling Peptides and Proteins
Cytokines
Tissue Inhibitor of Metalloproteinase-2
Tissue Inhibitor of Metalloproteinase-1
Aqueous Humor
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Interleukin-1
Extracellular Matrix
Oncostatin M
Tissue Inhibitor of Metalloproteinases
Fibroblast Growth Factor 1
Matrix Metalloproteinase 1
Metalloproteases
Endothelin-1
Mitogens
Epidermal Growth Factor

Keywords

  • Cytokine
  • Growth factor
  • Matrix metalloproteinase
  • Pig
  • TIMP
  • Trabecular meshwork

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

Cite this

Growth factor and cytokine modulation of trabecular meshwork matrix metalloproteinase and TIMP expression. / Alexander, J. Preston; Samples, John R.; Acott, Ted.

In: Current Eye Research, Vol. 17, No. 3, 1998, p. 276-285.

Research output: Contribution to journalArticle

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N2 - Purpose. We hypothesize that regulated trabecular extracellular matrix (ECM) turnover, initiated by the matrix metalloproteinases, is critical for the maintenance of normal aqueous humor outflow rates. However, very little is known about the regulation of trabecular ECM turnover. To identify candidate trabecular regulators, we evaluated the effects of several growth factors and cytokines on trabecular matrix metalloproteinase and TIMP expression. Methods. Porcine trabecular meshwork cells were treated with several doses of a variety of growth factors and cytokines and culture media was analyzed after 24, 48 and 72 h. Zymograms were used to evaluate stromelysin, gelatinase A and B activity levels, while immunoblots of Western transfers were used to evaluate stromelysin, collagenase, TIMP-1 and TIMP-2 protein levels. Results. A phorbol mitogen (TPA), TNFα and β, interleukin-1α and PDGF BB stimulate gelatinase B, stromelysin, interstitial collagenase and TIMP-1 expression, while having negligible effects on gelatinase A expression; TIMP-2 levels are reduced by TNF but not affected by the other treatments. Acidic and basic FGF, IL-1β, TGFβ and PDGF AB produce similar but smaller effects, while HGF, VEGF, EGF, KGF and LIF produce small to moderate elevations in stromelysin with minimal other responses. PDGF AA, γINF, oncostatin-M and endothelin-1 produce negligible changes in these proteinases and inhibitors. Conclusions. In addition to providing potential ways to modulate trabecular metalloproteinase and TIMP levels, the responsiveness of these cells to some of these growth factors and cytokines suggests possible roles in normal or pathogenic trabecular cell regulation and some may affect aqueous humor outflow.

AB - Purpose. We hypothesize that regulated trabecular extracellular matrix (ECM) turnover, initiated by the matrix metalloproteinases, is critical for the maintenance of normal aqueous humor outflow rates. However, very little is known about the regulation of trabecular ECM turnover. To identify candidate trabecular regulators, we evaluated the effects of several growth factors and cytokines on trabecular matrix metalloproteinase and TIMP expression. Methods. Porcine trabecular meshwork cells were treated with several doses of a variety of growth factors and cytokines and culture media was analyzed after 24, 48 and 72 h. Zymograms were used to evaluate stromelysin, gelatinase A and B activity levels, while immunoblots of Western transfers were used to evaluate stromelysin, collagenase, TIMP-1 and TIMP-2 protein levels. Results. A phorbol mitogen (TPA), TNFα and β, interleukin-1α and PDGF BB stimulate gelatinase B, stromelysin, interstitial collagenase and TIMP-1 expression, while having negligible effects on gelatinase A expression; TIMP-2 levels are reduced by TNF but not affected by the other treatments. Acidic and basic FGF, IL-1β, TGFβ and PDGF AB produce similar but smaller effects, while HGF, VEGF, EGF, KGF and LIF produce small to moderate elevations in stromelysin with minimal other responses. PDGF AA, γINF, oncostatin-M and endothelin-1 produce negligible changes in these proteinases and inhibitors. Conclusions. In addition to providing potential ways to modulate trabecular metalloproteinase and TIMP levels, the responsiveness of these cells to some of these growth factors and cytokines suggests possible roles in normal or pathogenic trabecular cell regulation and some may affect aqueous humor outflow.

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