Apolipoprotein E Regulates Primary Cultured Human Mesangial Cell Proliferation

Abstract

Background: The role of apolipoprotein (apo) E in kidney disease is still unclear. Animal studies have been performed, but it is doubtful if the conclusions are applicable to human beings. The objective of this study was to determine how apo E acts on human kidneys using primary cultured normal human mesangial cells (NHMCs) rather than animals used in previous studies. Methods: apo E and its isoforms E2, E3 and E4, or combinations with apo B were cocultured with primary NHMCs in serum-free medium. Premix WST-1 Cell Proliferation Assay System and DNA-Prep Reagent System were used to measure the proliferation and apoptosis of NHMCs, respectively. Results: (1) apo E itself increased NHMC proliferation at 24 h of culture, while it inhibited this proliferation after 48 h. (2) At 72 h of culture, apo E alone inhibited NHMC proliferation at concentrations higher than 0.78 µg/ml in concentration-dependent manner. (3) When co-cultured with both apo E and apo B, NHMC proliferation was higher than that with apo E alone and lower than that with apo B alone. (4) At 72 h of culture, apo E2, E3 and E4 inhibited NHMC proliferation at different intensities, with no proliferative effect observed. (5) Neither apo E nor apo B caused NHMC apoptosis. Conclusion: apo E regulates primary NHMC proliferation by (1) inhibiting NHMC proliferation or reducing NHMC proliferation induced by apo B, which implies that apo E has a protective effect on the kidney, and (2) increasing the proliferation under certain conditions.

apoE Expression in Glomerulus and Correlation with Glomerulosclerosis Induced by Adriamycin in Rats

“…19 Investigators reported that the apoE took a protective role for kidney. 3,4 Some other investigations found that the apoE expression in renal glomerulus was elevated when compared with that of the normal group; 5-7 however, those studies did not explore the relation between apoE and Col-IV, FN, TGF-b1, and a-SMA. The deposition of lipids in glomeruli, as an important pathogenetic factor, involves in glomerular sclerosis and leads to progression of renal disease.…”

“…The GSI was calculated according to the method of Raij et al 9 The severity of the lesions in a minimum of 40 glomeruli (range 40-80) in each specimen was examined, graded from 0 to 4 points in accordance with the percentage of morphological changes on each glomerulus (0 = 0%, 1 += 1-25%, 2 += 26-50%, 3 += 51-75%, 4 += 76-100%). The number of glomeruli showing a lesion of 0 was n 0 , of 1+ was n 1 , of 2+ was n 2 , of 3+ was n 3 , of 4+ was n 4 . Forty (range 40-80) glomeruli were examined independently, and the average score of each specimen was then calculated.…”

“…Investigators reported that the apoE took a protective role for kidney. 3,4 Some other investigations found that the apoE expression in renal glomerulus was elevated when there were some renal diseases. [5][6][7][8] However, the available evidence reported to date is weak, due to small sample number in those studies to some extent, especially for some clinical studies.…”

Proinflammatory Effects of C-Peptide in Different Tissues

“…Elevated levels of albumin in urine serve as clinical predictors of diabetic nephropathy [42]. Apolipoprotein E modulates human mesangial cell proliferation depending on the length of stimulation and cell conditions [43]. It has been shown that mice with increased hyperlipidemia in plasma have an increased progression of renal disease [44].…”