Nephron-specific expression of components of the renin–angiotensin–aldosterone system in the mouse kidney

Abstract

Introduction:The renin-angiotensin-aldosterone system (RAAS) plays an integral role in the regulation of blood pressure, electrolyte and fluid homeostasis in mammals. The capability of the different nephron segments to form components of the RAAS is only partially known. This study therefore aimed to characterize the nephron-specific expression of RAAS components within the mouse kidney. Materials and methods: Defined nephron segments of adult C57B/16 mice were microdissected after collagenase digestion. The gene expression of renin, angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin II receptors 1a (AT1a), 1b (AT1b), and 2 (AT2) was assessed by reverse transcriptase polymerase chain reaction (RT-PCR). Results: Renin mRNA was present in glomeruli, in proximal tubules, in distal convoluted tubules (DCT) and cortical collecting ducts (CCD). AGT mRNA was found in proximal tubules, descending thin limb of Henle's loop (dTL) and in the medullary part of the thick ascending limb (mTAL). ACE mRNA was not detectable in microdissected mouse nephron segments. AT1a, AT1b and AT2 mRNA was detected in glomeruli and proximal convoluted tubules.Conclusions: Our data demonstrate a nephron-specific distribution of RAAS components. All components of the local RAAS -except ACE -are present in proximal convoluted tubules, emphasizing their involvement in sodium and water handling.

Association of Elevated Urinary Concentration of Renin-Angiotensin System Components and Severe AKI

“…Importantly, the source of urinary angiotensinogen and renin during AKI remains unclear. However, both of these genes are expressed in both the proximal and distal tubule, and both proteins have been detected in the proximal tubule (38,39).…”

Intrarenal Renin–Angiotensin System Involvement in the Pathogenesis of Chronic Progressive Nephropathy—Bridging the Informational Gap Between Disciplines

“…78 –80 All of the components necessary to generate intrarenal AngII are present within the interstitial and intratubular compartments of the kidney involving multiple independent mechanisms, including classic RAS pathways, (pro)-renin receptors (PRRs), and chymase (Figure 2). 60,69,70,81 –110 In addition, intrarenal AngII positively augments other components of IRAS, such as proximal tubular angiotensinogen (AGT), collecting duct renin, and tubular AT1Rs. 69 Alternative processing of AngI or further processing of AngII by other enzymes (chymase, cathepsins, neprilysin, angiotensin-converting enzyme 2 [ACE2]) can lead to the formation of biologically active angiotensin-related peptides (AngIII, AngIV, Ang[1-7], Ang[1-9]) that activate alternative receptors in a series of signal amplification steps (AngII type 2 receptor [AT2R], Mas receptor [MasR], mas-related G-protein–coupled receptor [MrgD], AngII type 4 receptor [AT4R]).…”

Compensatory regulation of Na+ absorption by Na+/H+ exchanger and Na+-Cl- cotransporter in zebrafish (Danio rerio)

“…The remaining sodium is reabsorbed by the distal convoluted tubules and the collecting ducts, via Na + -Cl - cotransporters (NCC) and epithelial sodium channels (ENaC), respectively [1]. Hormonal control of sodium reabsorption occurs primarily in the distal convoluted tubules and the collecting ducts [2], suggesting that while NHE performs the majority of sodium reabsorption, this process is fine-tuned by NCC and ENaC in the mammalian kidney. Sodium transport along the nephron can be regulated through controlling the abundance, activity, and subcellular distribution of transporters [3].…”