Effects Of Valsartan On Scavenger Receptor MRNA Expression In Human Mesangial Cells

Background:It is well-known that deposition of lipoprotein accelerate glomerulosclerosis. oxidized low density lipoprotein(OX-LDL) may contribute to the pathogenesis of glomerulosclerosis by stimulating mesangial cells inflammatory response and secreting adhesive factor, inducing apoptosis of HMC by generating oxygen-derived free radidicals, enhancing fibronectin laminin protein synthesis and gene expression of extracellular matrix protein while HMC will lead to necrosis directly in high concentration OX-LDL.Finaly, normal structure of glomerulus are destroyed and loss of function is inevitable.It's unclear how HMC uptake OX-LDL. Recent study found HMC could express an inducible scavenger receptors (SR) , whichwas essantial to mediate the uptake of modified low-density lipoproteins. SR was not reguleted by concentration in the cell.There was no report how to decrease deposition of OX-LDL in the cell by down-regulation of SR expression.Angiotensin II receptor blocker(ARB) has been widely used in renal disease. It delayed glomerulosclerosis by ellaviated hemodynamics, down-regulated expression of TGF-B, inhibited secretion of ECM and facilitated degeneration of ECM by blockage of Angiotensin II receptor.lt remains unclear whether ARB down-regulate the SR expression in HMC. Purpose:(1) We use Phorbol 12-Myristate 13-acetate(PMA) as agitator to observe SR expression in HMC (2)we investigated SR expression after HMC were cultured in valsartan rat serum . Methods:HMC were cultured in vitra . Level of SR expression was assessed by flow cytometry analysis and RT-PCR after treated with PMA .RT-PCR products were purified, sequenced and compared with data of human macrophage gene bank.High SR expression HMCwere selected to cultured in different concentration of valsartan rat serum or in the same concentration but in different treatment time. Level of SR mRNA were exiamined. Results:SR mRNA in HMC was increased in dose-dependant manner when PMA treatment .The RT-PCR products were the same as the sequence of SR mRNA in macrophages. Valsartan could down-regulate SR mRNA expression in dose-dependant and time-dependant manner. Conclusion:Our experiment indicate that SR can be expressed in HMC and will up-regulate in case of PMA treatment. It may be one cause of reason why lipoprotein deposit in glomerulus. Valsartan can down-regulate remarkedly SR mRNA expression.