Abstract
The (pro)renin receptor is a multifunctional protein with roles in angiotensin-II-dependent and -independent intracellular cell signaling and roles as an intracellular accessory protein for the vacuolar H+-ATPase, including hormone secretion. While (pro)renin receptor mRNA is widely expressed in various human tissues, localization of (pro)renin receptor protein expression has not yet been systemically determined. Therefore, this study localized (pro)renin receptor protein expression in human organs. Systemic immunohistochemical examination of (pro)renin receptor expression was performed in whole body organs of autopsy cases. (Pro)renin receptor immunostaining was observed in the cytoplasm of cells in almost all human organs. It was observed in thyroid follicular epithelial cells, hepatic cells, pancreatic duct epithelial cells, zona glomerulosa and zona reticularis of the cortex and medulla of the adrenal gland, proximal and distal tubules and collecting ducts of the kidney, cardiomyocytes, and skeletal muscle cells. In the brain, (pro)renin receptor staining was detected in neurons throughout all areas, especially in the medulla oblongata, paraventricular nucleus and supraoptic nucleus of the hypothalamus, cerebrum, granular layer of the hippocampus, Purkinje cell layer of the cerebellum, and the pituitary anterior and posterior lobes. In the anterior lobe of the pituitary gland, all types of anterior pituitary hormone-positive cells showed double staining with (pro)renin receptor. These data showed that (pro)renin receptor protein was expressed in almost all organs of the human body. Its expression pattern was not uniform, and cell-specific expression pattern was observed, supporting the notion that (pro)renin receptor plays numerous physiological roles in each human organ.
Highlights
Academic Editor: Muhammad Shahab erenin receptor is a multifunctional protein with roles in angiotensin-II-dependent and -independent intracellular cell signaling and roles as an intracellular accessory protein for the vacuolar H+-ATPase, including hormone secretion
Introduction erenin receptor ((P)RR) consisting of 350 amino acids with a single transmembrane domain binds preferentially to renin and prorenin [1]. e binding of prorenin to the (P)RR leads to nonproteolytic renin activation [2], which induces the conversion of angiotensinogen to angiotensin (Ang) I. is process plays a key role in the regulation of the tissue renin-angiotensin system (RAS) [1]. e (P)RR stimulates its own intracellular tyrosine-phosphorylationdependent pathways, such as mitogen-activated protein kinase (MAPK) [1] and extracellular-signal-regulated kinase 1 and 2 (ERK1 and ERK2) [3], independent of RAS activation
V-ATPase has a function in secreting hormones and membrane fusion, independent of acidification [5,6,7]. e (P)RR works as an adaptor protein between the V-ATPase and Wnt receptor complex [8], which is involved in virtually every aspect of embryonic development and in homeostatic self-renewal [9]
Summary
E double immunostaining was performed as follows: (1) sections were incubated with (P)RR antibody; (2) binding of antibody was visualized with DAB by the PIC method; (3) immunohistochemical images were microphotographed; (4) sections were rinsed in PBS to preserve DAB pigments; (5) sections were processed with 1% hydrochloric acid 70% alcohol for removal of the GH antibody or adrenocorticotropic hormone (ACTH) antibody, secondary antibody, and hematoxylin and processed by microwave treatment to remove luteinizing hormone (LH) antibody, follicle-stimulating hormone (FSH) antibody, thyroid-stimulating hormone (TSH) antibody, or prolactin (PRL) antibody, secondary antibody, and hematoxylin; (6) sections were incubated with anterior pituitary hormone antibodies; (7) binding of antibody was detected using DAB-NiCl2 by the PIC method after DAB; and (8) immunohistochemical observations were compared with images at the same positions as those in the initial pictures. Identical sections were double-immunostained for anterior pituitary hormones. e double immunostaining was performed as follows: (1) sections were incubated with (P)RR antibody; (2) binding of antibody was visualized with DAB by the PIC method; (3) immunohistochemical images were microphotographed; (4) sections were rinsed in PBS to preserve DAB pigments; (5) sections were processed with 1% hydrochloric acid 70% alcohol for removal of the GH antibody or adrenocorticotropic hormone (ACTH) antibody, secondary antibody, and hematoxylin and processed by microwave treatment to remove luteinizing hormone (LH) antibody, follicle-stimulating hormone (FSH) antibody, thyroid-stimulating hormone (TSH) antibody, or prolactin (PRL) antibody, secondary antibody, and hematoxylin; (6) sections were incubated with anterior pituitary hormone antibodies; (7) binding of antibody was detected using DAB-NiCl2 by the PIC method after DAB; and (8) immunohistochemical observations were compared with images at the same positions as those in the initial pictures. e immunostaining intensity in the cytoplasm was evaluated on a scale of − (no staining), ± (borderline staining), and + (positive staining)
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