Apolipoprotein E regulates primary cultured human mesangial cell proliferation.
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 microg/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.


CONCLUSIONS
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.
Zhang
Yixiang
Y
Second Division of Internal Medicine, Medical Faculty, Kagoshima University, Kagoshima, Japan.
Yasumoto
Yuichiro
Y
Ikeda
Toru
T
Takenouchi
Syozo
S
Sogabe
Atsushi
A
Nosaki
Tsuyoshi
T
Che
Xiaofang
X
Zheng
Chunlei
C
Haraguchi
Misako
M
Akiyama
Shin-ichi
S
Tsubouchi
Hirohito
H
D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001055:Apolipoproteins B / Q000494:pharmacology; D001057:Apolipoproteins E / Q000494:pharmacology / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004338:Drug Combinations; D005920:Glomerular Mesangium / Q000166:cytology* / Q000502:physiology; D006801:Humans; D013997:Time Factors
D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D004338:Drug Combinations