Abstract
Background: The Apelin receptor (APJ)-Apelin system has been implicated in cardiovascular function but little is known regarding diabetic kidney disease. Apelin’s effects appear related, in part, to an interaction with angiotensin II. Apelin, like angiotensin II, is a substrate for ACE2, which we previously showed to localize in tubular and glomerular epithelial cells (podocytes). Here we wanted to investigate the localization of this peptide within the glomerulus and the overall expression of apelin and its receptor APJ within normal and diabetic mouse kidney. METHODS: We employed RT real time PCR, western blot, immunostaining, tissue and cell confocal microscopy to study apelin and APJ in kidneys from female C57BLKS mice (8 wks of age) and in cultured immortalized podocytes. Mouse podocytes were stimulated with Pyr 1 Apelin-13 (100nM) for 0, 1, 5, 15 and 60min and tested for phospho-status of AKT, p70S6K and ERK. Kidneys from 8 weeks old db/db mice were also studied. Results: Both Apelin and APJ were abundantly present in the kidney being expressed in most glomerular tufts, proximal tubules, and arterioles. In glomeruli, apelin colocalized with nephrin, PECAM-1, and a-SMA indicating its presence in podocytes, endothelial cells, and mesangial cells. APJ, by contrast, did not colocalize with PECAM-1 but also colocalized with several podocyte markers. In the proximal tubule, the APJ receptor colocalized with ACE2. Apelin and APJ mRNA were also expressed in cultured mouse podocytes where apelin-13 induced AKT, p70S6K and ERK rapid signaling (at 15min). By RT real time PCR, kidney cortex from db/db mice (n=6) had reduced APJ (0.19±0.02 vs 0.62±0.08, p< 0.005) and pre-proapelin mRNA levels (0.12±0.08 vs 1.13±0.04, p< 0.001) as compared to db/m controls (n=6). Conclusions: Apelin and its receptor are widely expressed in the kidney, including podocytes where apelin-13 is involved in AKT, p70S6K and ERK signaling. Reduced apelinergic activity in the diabetic kidney could be possibly compensatory to the known overactivity of the RAS.
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