Actions of lipoproteins in cultured human mesangial cells: Modulation by mitogenic vasoconstrictors

E. F. Grone, H. E. Abboud, M. Hohne, A. K. Walli, H. J. Grone, D. Stuker, H. Robenek, E. Wieland, D. Seidel

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

Recent studies have suggested that hypercholesterolemia may aggravate glomerulosclerosis. Mesangial cells actively participate in this process. To elucidate mechanisms by which lipids act on human mesangial cells (HMC), we measured the receptor-specific uptake of apolipoprotein (Apo) B- and Apo B- and E-containing lipoproteins in the presence and absence of growth factors and studied the growth-related mechanisms in HMC after exposure to low- density lipoprotein (LDL). Human LDL and very low density β-lipoprotein (β- VLDL) isolated from cholesterol-fed rabbits were bound, internalized, and degraded by a receptor-specific mechanism (dissociation constants for degradation LDL 30.0 and for β-VLDL 4.1 μg protein/ml medium). Maximal capacities were 30-50% of those of human fibroblasts. Acetylated and copper- oxidized LDL were not taken up specifically, suggesting no active scavenger- receptor activity. Preexposure to endothelin-1 (5 x 10-7 M) and platelet- derived growth factor (PDGF A, B, 83 x 10-12 M) for 16 or 15 h, respectively, doubled the uptake of LDL by HMC. In addition, PDGF synergized with LDL in stimulating DNA synthesis. Exposure of HMC to LDL resulted in a transient elevation of mRNA that encodes c-fos and c-jun, with a maximal effect seen after 30-60 min. In addition, PDGF A- and B-chain mRNAs were transiently elevated, peaking at 3 h in response to LDL (25 μg protein/ml medium) and continued to increase in a concentration-dependent manner (25-75 μg protein/ml medium). These data demonstrate that HMC take up lipoproteins via a receptor-specific mechanism with a high affinity for Apo E-containing lipoproteins which are often found in plasma of patients with renal disease. Vasoconstrictor and mitogenic peptides enhance lipoprotein receptor activity and have a synergistic effect on the mitogenic effect of LDL. LDL stimulates a number of growth-related genes. These data suggest that lipoproteins may play a critical role in mediating mesangial cell hypertrophy or proliferation, events intimately involved in the development of glomerulosclerosis.

Original languageEnglish (US)
Pages (from-to)F686-F696
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume263
Issue number4 32-4
StatePublished - Jan 1 1992
Externally publishedYes

Keywords

  • glomerulosclerosis
  • growth-related genes
  • lipids
  • mesangial cell proliferation
  • platelet-derived growth factor

ASJC Scopus subject areas

  • Physiology

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