Figure.
Schematic illustration of the traditional and new functions of macula densa-derived prostaglandin E2 (PGE2). The sensing of reduced tubular [NaCl] via the furosemide-sensitive Na:2Cl:K (NKCC2) cotransporter leads to p38 and ERK1/2 (MAPK) signaling, increased PGE2 synthesis and release via cycloxygenase-2 (COX-2) and microsomal PGE synthase (mPGES) activation in macula densa (MD) cells. The paracrine action of MD-derived PGE2 causes renin release from juxtaglomerular (JG) renin cells (JGC) via the EP4 receptor (classic function). The newly emerging function of this MD/PGE2/EP4 axis is the recruitment of new renin cells into the JG apparatus (JGA) via the activation of CD44+ mesenchymal stem cell-like cells in the renal interstitium and their migration towards the JGA, and their differentiation into renin producing JGCs. AA: afferent arteriole, EA: efferent arteriole, G: glomerulus.