Human mesangial cells express inducible macrophage scavenger receptor

Background. Type A scavenger receptors (Scr) mediate the uptake of modified low-density lipoproteins by macrophages. The accumulation of lipids via th is process is thought to lead to foam cell formation in atherosclerotic pla ques. Human mesangial cells (HMCs) have not been previously shown to expres s Scr in normal culture. We therefore investigated whether there is an indu cible form of Scr in a human mesangial cell line (HMCL). Methods. Scr activity was analyzed by cellular uptake of fluorescently labe led acetylated low-density lipoprotein using a flow cytometer. Scr mRNA exp ression was examined using reverse transcription-polymerase chain reaction, followed by Southern blotting. To investigate the molecular mechanism of S cr expression, several reporter gene constructs were designed. The first co ntained a full Scr promoter, the second a part of the Scr promoter that has both AP-1 and ets transcription factor binding sites. Other constructs wer e identical to the second, except that they contained either AP-1 or ets mo tif mutations. Results. Phorbol 12-Myristate 13-acetate (PMA) and angiotensin II (Ang II) increased both the percentage of Scr-positive cells and the Scr mean fluore scence intensity. PMA and Ang II also increased Scr mRNA and promoter activ ity in a time-and dose-responsive manner. Protein kinase C and calmodulin t ransduction pathways were involved in Scr up-regulation induced by PMA and Ang II. Additionally, a serine/threonine kinase was involved in PMA stimula tion. Functional analysis showed that both AP-1 and ets motifs were specifi c response elements to PMA stimulation in HMCLs. Conclusions. This study suggests that HMCs may express an inducible Scr, by which cells can acquire lipids and convert to foam cells in developing glo merulosclerosis.