Megalin/LRP2 expression is induced by peroxisome proliferator-activated receptor -alpha and -gamma: implications for PPARs' roles in renal function

Megalin/LRP2 表达由过氧化物酶体增殖激活受体 -α 和 -γ 诱导:对 PPAR 在肾功能中的作用的影响

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作者:Felipe Cabezas, Jonathan Lagos, Carlos Céspedes, Carlos P Vio, Miguel Bronfman, María-Paz Marzolo

Background

Megalin is a large endocytic receptor with relevant functions during development and adult life. It is expressed at the apical surface of several epithelial cell types, including proximal tubule cells (PTCs) in the kidney, where it internalizes apolipoproteins, vitamins and hormones with their corresponding carrier proteins and signaling molecules. Despite the important physiological roles of megalin little is known about the regulation of its expression. By analyzing the human megalin promoter, we found three response elements for the peroxisomal proliferator-activated receptor (PPAR). The

Conclusions

PPARα/γ and their agonists positively control megalin expression. This regulation could have an important impact on several megalin-mediated physiological processes and on pathophysiologies such as chronic kidney disease associated with diabetes and hypertension, in which megalin expression is impaired.

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