Mitogenic signals for thrombin in mesangial cells: Regulation of phospholipase C and PDGF genes

P. J. Shultz, T. C. Knauss, P. Mene, H. E. Abboud

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62 Citations (Scopus)

Abstract

Thrombin is a proteolytic enzyme of diverse biological activities, which is produced during activation of the coagulation pathway. In addition, thrombin is a mitogen for fibroblasts and endothelial cells. Intraglomerular thrombosis and cell proliferation are common pathological features of several glomerular diseases. We studied the effect of thrombin on deoxyribonucleic acid (DNA) synthesis in cultured human mesangial cells and explored mechanisms of signal transduction involved. Bovine and human thrombin caused dose-dependent increases in DNA synthesis, inositol trisphosphate, and cytosolic calcium [(Ca2+)(i)]. A threefold increase in inositol-3-trisphosphate (IP3) levels was observed as early as 10 s after the addition of thrombin, whereas increases in (Ca2+)(i) occurred within 5-10 s and declined rapidly. Stimulation of mesangial cells by thrombin resulted in induction of messenger ribonucleic acids (mRNAs) encoding platelet-derived growth factor (PDGF) A- and B-chains. This was associated with an enhanced secretion of PDGF-like protein. These data provide mechanisms by which thrombin may regulate mesangial cell function in disease states.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume257
Issue number3
StatePublished - 1989
Externally publishedYes

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Mesangial Cells
Platelet-Derived Growth Factor
Type C Phospholipases
Thrombin
Genes
Inositol
Proto-Oncogene Proteins c-sis
DNA
Mitogens
Signal Transduction
Thrombosis
Peptide Hydrolases
Endothelial Cells
Fibroblasts
Cell Proliferation
RNA
Calcium

ASJC Scopus subject areas

  • Physiology

Cite this

Mitogenic signals for thrombin in mesangial cells : Regulation of phospholipase C and PDGF genes. / Shultz, P. J.; Knauss, T. C.; Mene, P.; Abboud, H. E.

In: American Journal of Physiology - Renal Fluid and Electrolyte Physiology, Vol. 257, No. 3, 1989.

Research output: Contribution to journalArticle

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