Pentosan polysulfate decreases proliferation and net extracellular matrix production in mouse mesangial cells

Sharon Elliot, Liliane J. Striker, William G. Stetler-Stevenson, Terry A. Jacot, Striker Gary E

Research output: Contribution to journalArticle

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Abstract

Glomerulosclerosis is characterized by extracellular matrix accumulation and is often associated with mesangial cell proliferation. Heparin-like molecules have been shown to decrease glomerulosclerosis in vivo, although their cellular site and mechanism of action is still unclear. In this study, a line of glomerular mesangial cells derived from normal mice was used to determine whether pentosan polysulfate (PPS) inhibited proliferation and altered extracellular matrix turnover. Cells treated with PPS showed a decrease in cell number beginning 24 h after treatment, which was maintained for 5 d. For matrix accumulation and degradation studies, cells were treated for 5 d and collagen types I and IV protein were measured by enzyme-linked immunosorbent assay as well as matrix metalloproteinases (MMP) measured by zymography. Collagen types I and type IV were significantly decreased in the media (P ≤ 0.0001) and cell layer (P ≤ 0.005) after treatment with PPS but not after treatment with heparin. By zymography, MMP-2 was significantly increased after treatment with PPS (P ≤ 0.001) and heparin (P ≤ 0.05). PPS and heparin also decreased MMP-9 (P ≤ 0.001) after treatment. Reverse zymography showed the presence of tissue inhibitors of metalloproteinases (TIMP)-1 and -2 in control mesangial cells. Treatment with PPS and heparin increased TIMP-1. In addition, TIMP-3 was found in the medium of treated but not control cells. In conclusion, PPS alters extracellular matrix turnover through the induction of MMP-2 and alterations in the TIMP profile and may be useful in decreasing progressive glomerulosclerosis.

Original languageEnglish
Pages (from-to)62-68
Number of pages7
JournalJournal of the American Society of Nephrology
Volume10
Issue number1
StatePublished - Jan 1 1999

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Pentosan Sulfuric Polyester
Mesangial Cells
Extracellular Matrix
Heparin
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase 2
Collagen Type I
Therapeutics
Tissue Inhibitor of Metalloproteinase-3
Tissue Inhibitor of Metalloproteinases
Tissue Inhibitor of Metalloproteinase-2
Collagen Type IV
Matrix Metalloproteinase 9
Matrix Metalloproteinases
Cell Count
Enzyme-Linked Immunosorbent Assay
Cell Proliferation

ASJC Scopus subject areas

  • Nephrology

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Pentosan polysulfate decreases proliferation and net extracellular matrix production in mouse mesangial cells. / Elliot, Sharon; Striker, Liliane J.; Stetler-Stevenson, William G.; Jacot, Terry A.; Gary E, Striker.

In: Journal of the American Society of Nephrology, Vol. 10, No. 1, 01.01.1999, p. 62-68.

Research output: Contribution to journalArticle

Elliot, Sharon ; Striker, Liliane J. ; Stetler-Stevenson, William G. ; Jacot, Terry A. ; Gary E, Striker. / Pentosan polysulfate decreases proliferation and net extracellular matrix production in mouse mesangial cells. In: Journal of the American Society of Nephrology. 1999 ; Vol. 10, No. 1. pp. 62-68.
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