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Effect of lipoproteins on cultured human mesangial cells
1Second Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Abstract:
It was recently reported that low-density lipoprotein (LDL) promotes mesangial cell proliferation, and oxidized LDL is cytotoxic for mesangial cells. However, there have been few studies about the effects of other lipoproteins on mesangial cells. Accordingly, we investigated the effect of various lipoproteins on cultured human mesangial cells using 3H-thymidine (3H-TdR) incorporation and cell counting assays. We also investigated the levels of several cytokines in mesangial cell culture supernatants after stimulation by the lipoproteins. Addition of very-low-density lipoprotein (VLDL) at concentrations up to 100 micrograms/mL, intermediate-density lipoprotein (IDL) at up to 50 micrograms/mL, and LDL at up to 50 micrograms/mL induced the proliferation of cultured human mesangial cells, whereas cell growth was inhibited at higher concentrations. Oxidized LDL caused a concentration-dependent decrease of 3H-TdR incorporation. High-density lipoprotein (HDL) had no proliferative effective effect at any concentration. Exposure to VLDL, IDL, LDL, or a high concentration of HDL enhanced the secretion of interleukin-6, platelet-derived growth factor, and transforming growth factor-beta by mesangial cells, whereas tumor necrosis factor-alpha secretion was stimulated by oxidized LDL. These finding indicate that triglyceride (TG)-rich lipoproteins (VLDL and IDL) promote mesangial cell proliferation as well as LDL, whereas oxidized LDL has the reverse effect. These effects of lipoproteins may be related to modulation of various cytokines. Accordingly, TG-rich lipoproteins, LDL, and oxidized LDL may be involved in mesangial cell proliferation and injury in patients with mesangial proliferative glomerulonephritis.
Insights
Triglyceride-rich lipoproteins (VLDL, IDL) and LDL promote mesangial cell proliferation, while oxidized LDL inhibits it. Lipoproteins modulate cytokine secretion, potentially impacting mesangial cell injury in glomerulonephritis.
Area of Science:
- Nephrology
- Lipid Metabolism
- Cell Biology
Background:
- Low-density lipoprotein (LDL) is known to affect mesangial cells.
- Limited research exists on other lipoproteins' impact on mesangial cells.
Purpose of the Study:
- To investigate the effects of various lipoproteins on cultured human mesangial cells.
- To analyze the impact of lipoproteins on cytokine secretion by mesangial cells.
Main Methods:
- Utilized 3H-thymidine incorporation and cell counting assays.
- Measured cytokine levels (IL-6, PDGF, TGF-β, TNF-α) in mesangial cell culture supernatants.
- Tested very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), LDL, oxidized LDL, and high-density lipoprotein (HDL).
Main Results:
- VLDL, IDL, and LDL (at specific concentrations) induced mesangial cell proliferation.
- Oxidized LDL demonstrated a concentration-dependent inhibition of proliferation.
- Lipoproteins modulated the secretion of various cytokines, including IL-6, PDGF, TGF-β, and TNF-α.
Conclusions:
- Triglyceride-rich lipoproteins (VLDL, IDL) and LDL promote mesangial cell proliferation, contrasting with oxidized LDL's inhibitory effect.
- Lipoprotein-induced cytokine modulation may play a role in mesangial cell proliferation and injury.
- These findings suggest potential involvement of lipoproteins in mesangial proliferative glomerulonephritis.