Renin Similar to the Submaxillary Gland form is Expressed in Mouse Mesangial Cells: Subcellular Localization and AII Generation Under Control and Glucose-Stimulated Conditions

Abstract

It was analyzed the forms of renin produced by a mouse immortalized mesangial cell line (MIC) and their ability to generate angiotensin II (AII). The synthesis, localization and secretion of renin and AII by MIC were evaluated under conditions of normal (10 mM) or high (30 mM) glucose concentration. Two major bands of 35 kDa and 70 kDa were observed in SDS-PAGE. The amino-terminal sequencing reveled the presence of prorenin and renin in these bands with higher homology with the submaxillary gland form of renin. Renin and AII were detected in cell lysate and in culture medium, indicating that MIC synthesize and secrete these peptides. Renin was localized in the cytoplasm while AII was seen predominantly inside the nucleus. High glucose induced an increase in the synthesis and secretion of renin and AII. Results suggest that MIC produce AII and a renin form similar to the submandibular. Intracellular AII may be directed at the nucleus and/or be secreted, indicating that AII may directly influences gene expression in these cells. The mechanisms of synthesis and secretion of renin and AII are potentially modified by high glucose concentration, suggesting a possible role of AII produced by mesangial cells in diabetic nephropathy.

New insights into the renoprotective actions of the renin inhibitor aliskiren in experimental renal disease

“…Gene and protein expression of angiotensinogen (Aogen), renin and ACE has been reported in cultured glomerular mesangial cells [12][13][14][15][16][17][18][19][20][21][22][23][24] and podocytes. [25][26][27][28] Mesangial expression of Aogen and ACE has also been documented in renal tissue sections.…”

“…However, some of the label seen in glomeruli may have reflected aliskiren bound to renin that possibly was present in the mesangial matrix. In addition, as aliskiren can penetrate cultured cardiomyocytes, 98 the drug may have entered mesangial cells and podocytes, both of which express renin 20,[24][25][26] to which aliskiren could bind. Furthermore, the unequivocal evidence for labeled aliskiren in the walls of renal vessels prompts the proposal that this DRI can enter JG cells, and possibly incorporate into forming or formed renin granules.…”

Expression of angiotensin I-converting enzymes and bradykinin B2 receptors in mouse inner medullary-collecting duct cells

“…The components of renin-angiotensin system (RAS) in the kidney were described in the mesangial cells (MC) [2][3][4][5][6][7] indicating an important function in the cell contraction that could change the glomerular hemodinamic, but, there is evidence of an intratubular RAS in the control of salt and water transport [8]. The presence of all functional components of RAS in the proximal tubule is well known [9], but recently the presence of renin in the cortical and medullary ducts was described [10] and of ACE which was demonstrated to be secreted into the tubular lumen of the collecting duct in the distal portion of the nephron able to produce AII and inactivate kinin [2].…”

Renin-angiotensin system in the kidney: What is new?

“…It is thought that intracellular Ang Ⅱ levels could be altered in different diseases, such as diabetic nephropathy and cardiomyopathy, where hyperglycemia might induce intracellular Ang Ⅱ production. Indeed, a high glucose concentration induced an increase of ACE mRNA, synthesis and secretion of renin and Ang Ⅱ in an immortalized murine mesangial cell line [117][118][119] . Interestingly, an alternative pathway was found for the synthesis of intracellular Ang Ⅱ in the presence of high glucose in vascular smooth muscle cells.…”