High Lipid-mediated Endoplasmic Reticulum Stress In Human Glomerular Mesangial Cell Injury Under Inflammation Condition: The Role And Mechanisms

Objective: To study the role of high lipid-mediated endoplasmicreticulum stress in human glomerular mesangial cells (HMCs) injury underinflammation condition, and to explore the mechanism of lipid-inducedkidney injury.Methods: HMCs was divided into control group, high lipid group,inflammatory stress group, high lipid plus inflammatory stress group or4-phenylbutyric acid (4-PBA) group. After culture for24h,48h, and72h,Oil red O staining was used to evaluate lipid droplet accumulation in thecells; cell proliferation was assessed by MTT assay; expression of GRP78protein was measured by immunocytochemistry method and Western-blottassay; the levels of GRP78and FN mRNA were examined by real-timePCR.Results：（1）Compared with control group, the high lipid group, inflammatory stress group and high lipid plus inflammatory stress group hadsignificantly increased intracellular cholesterol levels (all0.01),significantly higher FN mRNA levels (all0.01), and significantly fastercell proliferation (all0.01), which was in a time-dependent manner.Compared with high lipid plus inflammatory stress group,4-PBA group hadsignificantly reduced lipid deposition (all0.01), slower cell proliferation(all0.01) and lower FN mRNA expression (0.05，0.01) induced byhigh lipid.（2） Compared with control group, high lipid group,inflammatory group and high lipid plus inflammatory stress group hadsignificantly increased expression of GRP78mRNA and protein (p<0.05，p<0.01), and the expression in4-PBA treatment group was significantlylower than that in the high lipid plus inflammatory stress group (all p<0.01).（3）Aftertreatmentwithhighlipidorinflammationfor24,48and72h,theintracellular cholesterol level was positively correlated with mesangial cellproliferation, and expression of GRP78protein and FN mRNA (all p<0.01).The cellular expression of GRP78was positively correlated with mesangialcell proliferation and FN mRNA expression (all p<0.05).Conclusion: High lipid can induce glomerular mesangial cell injurythrough activating endoplasmic reticulum stress in HMCs underinflammation stress condition. Reducing ER stress may present a way to attenuate cell injury. Such studies will further provide a foundation forclinical research of renal diseases.