Jian-Pi-Yi-Shen Regulates EPO and Iron Recycling Protein Expressions in Anemic Rats with Chronic Kidney Disease: Accumulation of Hypoxia Inducible Factor-2α via ERK Signaling

Autor: Fochang Wang, Huimin Yu, Zhang Shangbin, Shunmin Li, Zheng Ping, Jianping Chen, Shiying Huang, Lin Zheng
Rok vydání: 2020
Předmět:
Zdroj: Evidence-Based Complementary and Alternative Medicine, Vol 2020 (2020)
ISSN: 1741-4288
1741-427X
Popis: Background: Jian-Pi-Yi-Shen (JPYS), the traditional Chinese medicine (TCM) decoction has been commonly used to treat chronic kidney disease (CKD) and its complications such as anemia. JPYS has been previously found to induce erythropoietin (EPO) production in HEK293T cells and CKD rats. However, the mechanism of JPYS in treating anemia of CKD rats has remained largely unknown. Here, we further extend our effort to investigate the translational control of hypoxia inducible factor (HIF)-α protein via ERK signaling and the effect on iron recycling related protein expression by JPYS, thus revealing the mechanism of JPYS in correcting anemia in CKD. Methods: Experimental CKD rats with anemia were induced by 5/6 nephrectomy. Rats were administrated orally with high dose (6.0 g/kg/d) and low dose ( 1.5 g/kg/d ) of JPYS for 90 days. Serum hepcidin level was determined to evaluate iron homeostasis. Protein expressions of HIF-2α, erythropoietin (EPO), ferritin and ferroportin (FPN), as well as the phosphorylation level of extracellular signal regulated kinase 1/2 (RK1/2) were detected by Western blot. Results: Our data showed that JPYS treatment significantly ameliorated kidney function by reducing increased levels of blood urea nitrogen (BUN), serum creatinine (Scr) and the urine protein (UPRO). Periodic acid-Schiff (PAS) and Masson staining observation showed that the renal pathological damage was restored in JPYS-treated CKD rats. In parallel, JPYS markedly improved CKD anemia through up-regulation of red blood cell (RBC), hemoglobin (HGB) and haematocrit (HCT). JPYS stimulated EPO and HIF-2α protein expression in both kidney and liver of CKD rats. Furthermore, JPYS induced the phosphorylation of ERK1/2 protein. In addition, JPYS regulated protein expressions of ferritin and FPN in both liver and spleen of CKD rats, as well as serum level of hepcidin. Conclusions: JPYS induces the expression of EPO through ERK-mediated HIF-2α protein accumulation, and regulates systemic iron recycling, supporting its role in promoting erythropoiesis and improvement of anemia in CKD.
Databáze: OpenAIRE
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