C-type natriuretic peptide stimulates function of the murine Sertoli cells via activation of the NPR-B/cGMP/PKG signaling pathway

Abstract

C-type natriuretic peptide (CNP) is an important regulator of the male reproductive process. Our previous investigations showed that CNP can significantly stimulate the mRNA expression of androgen-binding protein (Abp) and transferrin (Trf) in the rat Sertoli cells, but the pathways responsible for this process remain to be elucidated. We predict that CNP binds the natriuretic peptide receptor B (NPR-B) to regulate expression of ABP and TRF through the intracellular cyclic guanosine monophosphate (cGMP) pathway. To address this question, in this study, we first confirmed the expression and localization of CNP and NPR-B in rat testes by immunohistochemistry and western blotting. Then, ELISA and real-time PCR were performed to investigate the signaling pathway of CNP in Sertoli cells in rat testes. Our results showed that CNP was mainly localized in the germ cells and Leydig cells, and its receptor, NPR-B, was mostly expressed in the Sertoli cells and vascular endothelial cells. CNP supplementation in the Sertoli cell medium was accompanied by an increase in the amount of intracellular cGMP and in the production of Abp and Trf mRNA, whereas inhibition of PKG with KT5823 led to a decrease in the expression of Abp and Trf mRNA. Moreover, Abp and Trf mRNA were no longer elevated when we used liposome-mediated RNA interference technology to silence the NPR-B gene in a mouse Sertoli cell line (TM4). These results suggest that CNP contributes to the regulation of ABP and TRF in the Sertoli cells through the NPR-B/cGMP/PKG signaling pathways.

Efficiency of C-type natriuretic peptide on improvement of Iraqi local ram’s epididymal sperms

“…Based on PCR analyses at different times of cooling intervals, the findings of the current study showed that the expression of the hNPR-B gene was elevated significantly in CNP samples in comparison with controls. Our findings are in agreement with those demonstrated by other researchers ( Ueda et al ., 2020 ; Yu et al ., 2021 ; Nakagawa and Nishikimi, 2022 ). NPR-B is a guanylate cyclase-linked receptor that appears to be activated CNP ( Pagel-Langenickel et al ., 2007 ).…”

Glucocorticoids ameliorate cardiorenal syndrome through the NPR1/SGK1 pathway in natriuretic peptide receptor A‑heterozygous mice

“…Members of the natriuretic peptide (NP) family, such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), serve important physiological functions in maintaining cardiovascular homeostasis ( 1 , 2 ). ANP and BNP are primarily synthesized in the heart tissues and circulate in blood, while CNP is mainly produced by vascular endothelial cells and may mediate physiological effects, such as cardiomyocyte contractility, reproduction, cell proliferation ( 2 , 3 ). These peptides exert their effects by binding to NP receptors (NPRs) 1, 2 and 3.…”

“…These peptides exert their effects by binding to NP receptors (NPRs) 1, 2 and 3. NPR1, which binds to ANP and BNP, and NPR-B, which is selective for CNP, ( 2 , 3 ) are composed of an extracellular ligand-binding, a transmembrane, an intracellular kinase homology and a C-terminal guanylate cyclase domain ( 4 ). In addition, NP-scavenging receptor (also known as NPR-C) lacks guanylate cyclase activity and mediates NP degradation ( 5 ).…”