Expression of (Pro)renin Receptor During Rapamycin-Induced Erythropoiesis in K562 Erythroleukemia Cells and Its Possible Dual Actions on Erythropoiesis

Abstract

(Pro)renin receptor ((P)RR), a specific receptor for renin and prorenin, is expressed in erythroblastic cells. (P)RR has multiple biological actions: prorenin activation, stimulation of the intracellular signaling including extracellular signal-regulated kinases, and functional complex formation with vacuolar H + -ATPase (v-ATPase). However, the functional implication of (P)RR in erythroblast cells has not been clarified. The aim of the present study was to clarify changes of (P)RR expression during erythropoiesis and a role of (P) RR in the heme synthesis. (P)RR expression was studied during rapamycin-induced erythropoiesis in a human erythroleukemia cell line, K562. Treatment with rapamycin (100 nM) for 48 hours significantly increased %number of hemoglobin-producing cells, γ -globin mRNA levels, erythroid specific 5-aminolevulinate synthase (ALAS2) mRNA levels, and heme content in K562 cells. Both (P)RR protein and mRNA levels increased about 1.4-fold during rapamycin-induced erythropoiesis. Suppression of (P) RR expression by (P)RR-specific small interference RNA increased ALAS2 mRNA levels about 1.6-fold in K562 cells, compared to control using scramble RNA, suggesting that (P)RR may down-regulate ALAS2 expression. By contrast, treatment with bafilomycin A1, an inhibitor of v-ATPase, decreased greatly % number of hemoglobin-producing cells and heme content in K562 cells, indicating that the v-ATPase function is essential for hemoglobinization and erythropoiesis. Treatment with bafilomycin A1 increased (P) RR protein and mRNA levels. In conclusion, we propose that (P)RR has dual actions on erythropoiesis: the promotion of erythropoiesis via v-ATPase function and the down-regulation of ALAS2 mRNA expression. Thus, (P)RR may contribute to the homeostatic control of erythropoiesis.

Expression of the Components of the Renin-Angiotensin System in Oncological Diseases

“…The results further studies confirm the thesis that the system (pro) renin -(pro) renin receptor has an important function in pathogenesis and progression of cancer (Shibayama Y. et al, 2015;Wang C. et al, 2016;Kaneko K. et al, 2017). No less relevant is the importance of information systems (pro) renin -(pro) renin receptor in the control of gene expression, regardless of the state PAC activity (Nguyen G., 2011;Müller DN et al, 2012.).…”

Expression of the Renin-Angiotensin System Components in Oncologic Diseases

“…No less relevant is the importance of the (pro)renin-(pro)renin receptor information systems in the control of gene expression, regardless of the state of RAS activity ( 52 , 53 ). The results of other studies confirm the thesis that the (pro)renin-(pro)renin receptor system has an important function in cancer pathogenesis and progression ( 54 , 69 , 70 , 72 , 73 ).…”

Long-term clinical spectrum and circulating RAS evaluation of anephric patients undergoing hemodialysis: A report of four cases and literature review

“… 16 It is noteworthy that recent studies have identified the expression of prorenin receptor (pRR), a specific receptor for renin and prorenin, in erythroid cells. 17 , 18 Overexpression of pRR leads to partial negative regulation of erythropoiesis in chronic inflammation. 5 Therefore, we speculate that the extremely low levels of PRA in anephric patients may lead to an insufficient combination of pRR on erythroid cells with renin, contributing to the amelioration of anemia, but the exact conclusion requires further study.…”