Megalin/LRP2 Expression Is Induced by Peroxisome Proliferator-Activated Receptor -Alpha and -Gamma: Implications for PPARs' Roles in Renal Function

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 objective of this study was to test whether megalin expression is regulated by the PPARs. METHODOLOGY/PRINCIPAL FINDINGS: Treatment of epithelial cell lines with PPARα or PPARγ ligands increased megalin mRNA and protein expression. The stimulation of megalin mRNA expression was blocked by the addition of specific PPARα or PPARγ antagonists. Furthermore, PPAR bound to three PPAR response elements located in the megalin promoter, as shown by EMSA, and PPARα and its agonist activated a luciferase construct containing a portion of the megalin promoter and the first response element. Accordingly, the activation of PPARα and PPARγ enhanced megalin expression in mouse kidney. As previously observed, high concentrations of bovine serum albumin (BSA) decreased megalin in PTCs in vitro; however, PTCs pretreated with PPARα and PPARγ agonists avoided this BSA-mediated reduction of megalin expression. Finally, we found that megalin expression was significantly inhibited in the PTCs of rats that were injected with BSA to induce tubulointerstitial damage and proteinuria. Treatment of these rats with PPARγ agonists counteracted the reduction in megalin expression and the proteinuria induced by BSA. 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

Hazard proximity and risk perception of tsunamis in coastal cities: Are people able to identify their risk?

Researchers have previously reported that hazard proximity can influence risk perception among individuals exposed to potential hazards. Understanding this relationship among coastline communities at risk of flood events caused by storms and/or tsunamis, is important because hazard proximity, should be recognized when planning and implementing preparation and mitigation actions against these events. Yet, we are not aware of studies that have examined this relationship among coastline inhabitants facing the risk of a tsunami. Consequently, the aim of this study was to examine the relationship between hazard proximity and perceived risk from tsunamis among coastline inhabitants. Participants were 487 residents of the coastal city of Iquique, Chile. They completed a survey during the spring of 2013 that assessed their perceived risk from several natural and non-natural hazards. We found that hazard proximity maintains a negative relationship with the perception of tsunami risk among coastline inhabitants. While this result confirms the general trend obtained in previous studies, this one is conclusive and significant. In contradiction with previous findings, we found that participants from the highest socioeconomic status reported the highest levels of risk perception. This finding can be explained by the fact that most participants from the highest socioeconomic status live closer to the coastline areas, so their risk perception reflects the place where they live, that is in a tsunami inundation zone. Once again, hazard proximity proved to be a determinant factor of risk perception. Our findings have important implications for the development of plans and programs for tsunami preparedness and mitigation. These indicate that individuals do use environmental cues to evaluate their own risk and can potentially make correct choices when having or not to evacuate. Also suggest that preparedness should incorporate how hazard proximity is recognized by individuals and communities at risk