Dataset Information

Recombinant Erythropoietin Provides Protection against Renal Fibrosis in Adenine-Induced Chronic Kidney Disease.

ABSTRACT: Chronic kidney disease (CKD) causes anemia by renal damage. In CKD, the kidney is submitted to hypoxia, persistent inflammation, leading to fibrosis and permanent loss of renal function. Human recombinant erythropoietin (rEPO) has been widely used to treat CKD-associated anemia and is known to possess organ-protective properties that are independent from its well-established hematopoietic effects. Nonhematopoietic effects of EPO are mediated by an alternative receptor that is proposed to consist of a heterocomplex between the erythropoietin receptor (EPOR) and the beta common receptor (?cR). The present study explored the effects of rEPO to prevent renal fibrosis in adenine-induced chronic kidney disease (Ad-CKD) and their association with the expression of the heterodimer EPOR/?cR. Male Wistar rats were randomized to control group (CTL), adenine-fed rats (Ad-CKD), and Ad-CKD with treatment of rEPO (1050?IU/kg, once weekly for 4 weeks). Ad-CKD rats exhibited anemia, uremia, decreased renal function, increased infiltration of inflammatory cells, tubular atrophy, and fibrosis. rEPO treatment not only corrected anemia but reduced uremia and partially improved renal function as well. In addition, we observed that rEPO diminishes tubular injury, prevents fibrosis deposition, and induces the EPOR/?cR heteroreceptor. The findings may explain the extrahematopoietic effects of rEPO in CKD and provide new strategies for the treatment of renal fibrosis in CKD.

SUBMITTER: Vazquez-Mendez E

PROVIDER: S-EPMC7063184 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Recombinant Erythropoietin Provides Protection against Renal Fibrosis in Adenine-Induced Chronic Kidney Disease.

Vázquez-Méndez Estefanía E Gutiérrez-Mercado Yanet Y Mendieta-Condado Edgar E Gálvez-Gastélum Francisco Javier FJ Esquivel-Solís Hugo H Sánchez-Toscano Yadira Y Morales-Martínez Claudia C Canales-Aguirre Alejandro A AA Márquez-Aguirre Ana Laura AL

Mediators of inflammation 20200227

Chronic kidney disease (CKD) causes anemia by renal damage. In CKD, the kidney is submitted to hypoxia, persistent inflammation, leading to fibrosis and permanent loss of renal function. Human recombinant erythropoietin (rEPO) has been widely used to treat CKD-associated anemia and is known to possess organ-protective properties that are independent from its well-established hematopoietic effects. Nonhematopoietic effects of EPO are mediated by an alternative receptor that is proposed to consist ...[more]

PMID: 32184703

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Project description:Helminths immunomodulate their hosts and induce a regulatory, anti-inflammatory milieu that prevents allergies and autoimmune diseases. Helminth immunomodulation may benefit sepsis outcome by preventing exacerbated inflammation and severe pathology, but the influence on bacterial clearance remains unclear. To address this, mice were chronically infected with the filarial nematode Litomosoides sigmodontis (L.s.) and the outcome of acute systemic inflammation caused by i.p. Escherichia coli injection was determined. L.s. infection significantly improved E. coli-induced hypothermia, bacterial clearance and sepsis survival and correlated with reduced concentrations of associated pro-inflammatory cytokines/chemokines and a less pronounced pro-inflammatory macrophage gene expression profile. Improved sepsis outcome in L.s.-infected animals was mediated by macrophages, but independent of the alternatively activated macrophage subset. Endosymbiotic Wolbachia bacteria that are present in most human pathogenic filariae, as well as L.s., signal via TLR2 and modulate macrophage function. Here, gene expression profiles of peritoneal macrophages from L.s.-infected mice revealed a downregulation of genes involved in TLR signaling, and pulsing of macrophages in vitro with L.s. extract reduced LPS-triggered activation. Subsequent transfer improved sepsis outcome in naïve mice in a Wolbachia- and TLR2-dependent manner. In vivo, phagocytosis was increased in macrophages from L.s.-infected wild type, but not TLR2-deficient animals. In association, L.s. infection neither improved bacterial clearance in TLR2-deficient animals nor ameliorated E. coli-induced hypothermia and sepsis survival. These results indicate that chronic L.s. infection has a dual beneficial effect on bacterial sepsis, reducing pro-inflammatory immune responses and improving bacterial control. Thus, helminths and their antigens may not only improve the outcome of autoimmune and allergic diseases, but may also present new therapeutic approaches for acute inflammatory diseases that do not impair bacterial control.

Dataset Information

Recombinant Erythropoietin Provides Protection against Renal Fibrosis in Adenine-Induced Chronic Kidney Disease.

Publications

Recombinant Erythropoietin Provides Protection against Renal Fibrosis in Adenine-Induced Chronic Kidney Disease.

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