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Abstract: Proximal tubule protein take‐up is interceded by 2 receptors, megalin and cubilin. These receptors rescue an assortment of filtered ligands including fundamental vitamins and hormones. The objective of this study was to investigate the potential relation of megalin receptor injury with nuclear factor‐kappa B (NF‐κB) upregulation in acute kidney injury rat model. Twenty four rats were allocated into two groups: control group received saline, while the second group was intoxicated with cadmium chloride (2.4 mg Cd/kg/day i.p) for 30 days. Blood urea nitrogen, serum creatinine, tissue oxidant–antioxidant parameters (malondialdehyde [MDA] and reduced glutathione [GSH]) and expression levels for NF‐κB, toll like receptor‐2 (TLR2), toll like receptor‐4 (TLR4), and megalin receptor were estimated. Noticeable downregulation of megalin receptor versus upregulation of NF‐κB, TLR2, and TLR4 were observed in AKI rat model together with significant elevation in MDA as well as significant reduction in GSH. The study concluded that the oxidative stress in kidney tissue leads to megalin receptor damage, which indeed motivates upregulation of NF‐κB through TLRs 2 and 4 pathways. [ABSTRACT FROM AUTHOR]

The kidney proximal tubule is a major target tissue of the renin-angiotensin system (RAS). Megalin is an endocytic multiligand receptor abundantly expressed in the proximal tubule where it drives reabsorption of peptides and proteins from the glomerular ultrafiltrate. All major RAS components are present in the kidney proximal tubules. Here, megalin drives endocytosis of angiotensinogen (AGT), prorenin, and renin, while angiotensin-converting enzyme is localised at the brush border of the proximal tubule cells. Intrarenal formation of the key RAS effector angiotensin II (ANG II) occurs, and liver-derived AGT appears to be the primary source. New studies further suggest that megalin-mediated reabsorption of liver-derived AGT contributes to renal ANG II levels and thereby may influence renal RAS activity. This mini-review presents the recent advances on RAS in the proximal tubule and the involvement of megalin in the uptake and regulation of local RAS and discusses the possibility that megalin is involved in blood pressure regulation., (© 2022 S. Karger AG, Basel.)