{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T21:34:35Z","timestamp":1778276075317,"version":"3.51.4"},"reference-count":58,"publisher":"American Physiological Society","issue":"3","funder":[{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["DK64324"],"award-info":[{"award-number":["DK64324"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000041","name":"American Diabetes Association (ADA)","doi-asserted-by":"publisher","award":["4-15-CKD-56"],"award-info":[{"award-number":["4-15-CKD-56"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2018,9,1]]},"abstract":"<jats:p> The prorenin receptor (PRR) was originally proposed to be a member of the renin-angiotensin system (RAS); however, recent work questioned their association. The present paper describes a functional link between the PRR and RAS in the renal juxtaglomerular apparatus (JGA), a classic anatomical site of the RAS. PRR expression was found in the sensory cells of the JGA, the macula densa (MD), and immunohistochemistry-localized PRR to the MD basolateral cell membrane in mouse, rat, and human kidneys. MD cell PRR activation led to MAP kinase ERK1\/2 signaling and stimulation of PGE<jats:sub>2<\/jats:sub> release, the classic pathway of MD-mediated renin release. Exogenous renin or prorenin added to the in vitro microperfused JGA-induced acute renin release, which was inhibited by removing the MD or by the administration of a PRR decoy peptide. To test the function of MD PRR in vivo, we established a new mouse model with inducible conditional knockout (cKO) of the PRR in MD cells based on neural nitric oxide synthase-driven Cre-lox recombination. Deletion of the MD PRR significantly reduced blood pressure and plasma renin. Challenging the RAS by low-salt diet + captopril treatment caused further significant reductions in blood pressure, renal renin, cyclooxygenase-2, and microsomal PGE synthase expression in cKO vs. wild-type mice. These results suggest that the MD PRR is essential in a novel JGA short-loop feedback mechanism, which is integrated within the classic MD mechanism to control renin synthesis and release and to maintain blood pressure. <\/jats:p>","DOI":"10.1152\/ajprenal.00029.2018","type":"journal-article","created":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T10:21:50Z","timestamp":1524046910000},"page":"F521-F534","source":"Crossref","is-referenced-by-count":46,"title":["The macula densa prorenin receptor is essential in renin release and blood pressure control"],"prefix":"10.1152","volume":"315","author":[{"given":"Anne D. 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