Localization of corin and atrial natriuretic peptide expression in human renal segments

Abstract

Atrial natriuretic peptide (ANP)-mediated natriuretic response is a well-established cardiac endocrine function. Corin is a transmembrane protease that activates ANP in the heart. Corin expression has been detected in non-cardiac tissues including the kidney. Here we examined corin, pro-ANP/ANP and natriuretic peptide receptor-A (NPR-A) expression in human renal segments. By immunostaining and in situ hybridization, we found similar corin, pro-ANP/ANP and NPR-A protein and mRNA expression in human renal segments. The expression was most abundant in the proximal convoluted tubules and the medullary connecting ducts. In the proximal tubules, corin protein was present in the apical membrane region underneath the brush border where the ANP-degrading protease neprilysin was abundant. These results suggest that corin-mediated pro-ANP activation may occur in renal segments and that locally produced ANP may act in an autocrine manner to regulate sodium and water reabsorption in situ. Our results also point to the proximal convoluted tubules as a major site for local ANP action. Such a renal corin/ANP autocrine mechanism may differ from the cardiac corin/ANP endocrine mechanism in regulating sodium homeostasis under physiological and pathological conditions.

Role of the protease corin in chondrogenic differentiation of human bone marrow‐derived mesenchymal stem cells

“…It functions as a key enzyme in the natriuretic peptide system by activating atrial natriuretic peptide, a cardiac hormone that regulates salt‐water balance and blood pressure (Zhou & Wu, ). In addition to the heart, corin is also expressed in non‐cardiac tissues, such as the pregnant uterus and kidneys, where it regulates uterine vessel remodelling and sodium reabsorption, respectively (Cui et al, ; Dong et al, ; Ichiki et al, ; Kaitu'u‐Lino et al, ; Polzin et al, ). These data indicate that corin may act in a tissue‐specific manner to participate in different physiological processes.…”

Clinical efficacy of dual inhibitor of neprilisin and AT1‑angiotensin receptors LCZ696 (sakubitril/valsartan) in chronic heart failure patients with impaired renal function

“…ПНП, сериновая протеаза, превращающая проПНП в активный пептид, НЭП и ГЦА-рецепторы экспрессированы в клетках нефрона, особенно в проксимальных канальцах и собирательных трубках, локализованных в мозговом веществе почек. Высокая плотность ГЦА-рецепторов обнаружена в подоцитах клубочков и гломерулярных мезангиаль-ных клетках [25][26][27]. Циркулирующие НУП и образу-ющийся локально ПНП прямо ингибируют реабсорб-цию натрия в проксимальном и дистальном сегментах нефрона, ослабляя стимулирующий эффект НА и АТ II [28], и способствуют увеличению СКФ, вызывая дилатацию прегломерулярных и сужение постгломе-рулярных артериол клубочков [29].…”

IL-1β increases urinary corin in patients with primary proteinuric kidney diseases and in 293 cells

“…Besides cardiomyocytes, corin has also been detected in the kidney. Corin is distributed in epithelial cells, including those of the proximal tubule, thick ascending limb, connecting tubule, and collecting duct, but not the glomerulus (12,22). The specific distribution of corin in the kidney suggests that corin may play a specific role in regulating kidney physiology.…”

“…In the kidney, corin was detected in epithelial cells, with segmental expression in the proximal tubule, thick ascending limb, connecting tubule, and throughout the collecting duct (12,22). Fang et al reported that the levels of urinary corin were markedly reduced in chronic kidney diseases, and that the reduction correlated with disease severity (23).…”

“…293 cells (26) were obtained from ATCC. 293-corin cells were stably transfected with pcDNA3.1-h corin (plasmid containing full-length human corin; Invitrogen, Carlsbad, USA) (27), which was constructed by the Cyrus Tang Medical Institute of Soochow University (Soochow, China) (9,22,28). In the present study, 293 corin cells were cultured in Dulbecco's modified Eagle's medium with 500 ng/ml G418, at 37˚C with 95% air and 5% CO 2 .…”