Dataset Information

MiR-146b-5p has a sex-specific role in renal and cardiac pathology in a rat model of chronic kidney disease.

ABSTRACT: Chronic kidney disease presents a complex and distinct pathological landscape in men and women, yet this difference is poorly understood. microRNAs are powerful molecular regulators of pathophysiology in the kidney and other organs. We previously reported a significant upregulation of miR-146b-5p in the 5/6 nephrectomy rat model of chronic kidney disease. Here we investigated the sex-specific contribution of miR-146b-5p to renocardiac pathology by generating a novel miR-146b^-/- rat and characterized the expression of miR-146b-5p in both wild-type and knockout animals. The 5/6 nephrectomy or sham surgery was performed on rats of each genotype and sex. Renal pathology was examined through gross histology, plasma and urinary analysis of electrolytes and metabolites, and by chronic blood pressure monitoring. Cardiac pathology was monitored via echocardiography and pressure-volume analysis. The miR-146b^-/- rats show functional knockout of miR-146b-5p in both the kidney and heart. While 5/6 nephrectomy induced tissue hypertrophy, miR-146b^-/- female rats displayed exacerbated renal hypertrophy. Additionally, miR-146b^-/- female rats exhibited a marked elevation of renal fibrosis and significant renal dysfunction yet lower blood pressure and less pronounced cardiac remodeling. These phenotypic differences were not exhibited in miR-146b^-/- male rats. Ovariectomy ameliorated renal pathology and abolished genotypic differences. In vitro examination of transforming growth factor-? signaling in combination with miR-146b-5p manipulation supports a role for miR-146b-5p in mediating the protective benefit of estrogen from renal pathologies. Thus, our data highlight an important role of miR-146b-5p in modulating kidney disease progression and provide new avenues for the study of sex-specific pathology.

SUBMITTER: Paterson MR

PROVIDER: S-EPMC6941490 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

miR-146b-5p has a sex-specific role in renal and cardiac pathology in a rat model of chronic kidney disease.

Paterson Mark R MR Geurts Aron M AM Kriegel Alison J AJ

Kidney international 20190816 6

Chronic kidney disease presents a complex and distinct pathological landscape in men and women, yet this difference is poorly understood. microRNAs are powerful molecular regulators of pathophysiology in the kidney and other organs. We previously reported a significant upregulation of miR-146b-5p in the 5/6 nephrectomy rat model of chronic kidney disease. Here we investigated the sex-specific contribution of miR-146b-5p to renocardiac pathology by generating a novel miR-146b<sup>-/-</sup> rat an ...[more]

PMID: 31668631

Similar Datasets

Project description:In the heart tissue of acutely Trypanosoma cruzi-infected mice miR-145-5p and miR-146b-5p are, respectively, downregulated and upregulated. Here, we used the H9C2 rat cardiomyoblast cell line infected with the Colombian T. cruzi strain to investigate the parasite-host cell interplay, focusing on the regulation of miR-145-5p and miR-146b-5p expression. Next, we explored the effects of interventions with the trypanosomicidal drug Benznidazole (Bz) alone or combined with Pentoxifylline (PTX), a methylxanthine derivative shown to modulate immunological and cardiac abnormalities in a model of chronic chagasic cardiomyopathy, on parasite load and expression of miR-145-5p and miR-146b-5p. The infection of H9C2 cells with trypomastigote forms allowed parasite cycle with intracellular forms multiplication and trypomastigote release. After 48 and 144 h of infection, upregulation of miR-145-5p (24 h: 2.38 ± 0.26; 48 h: 3.15 ± 0.9-fold change) and miR-146b-5b (24 h: 2.60 ± 0.46; 48 h: 2.97 ± 0.23-fold change) was detected. The peak of both miRNA levels paralleled with release of trypomastigote forms. Addition of 3 µM and 10 µM of Bz 48 h after infection reduced parasite load but did not interfere with miR-145-5p and miR-146b-5p levels. Addition of PTX did not interfere with Bz-induced parasite control efficacy. Conversely, combined Bz + PTX treatment decreased the levels of both microRNAs, resembling the expression levels detected in non-infected H9C2 cells. Moreover, the use of miR-145-5p and miR-146b-5p mimic/inhibitor systems before infection of H9C2 cells decreased parasite load, 72 h postinfection. When H9C2 cells were treated with miR-145-5p and miR-146b-5p mimic/inhibitor 48 h after infection, all the used systems, except the miR-146b-5p inhibitor, reduced parasite load. Altogether, our data indicate that these microRNAs putatively control signaling pathways crucial for parasite-host cell interaction. Thus, miR-145-5p and miR-146b-5p deserve to be further investigated as biomarkers of parasite control and tools to identify therapeutic adjuvants to etiological treatment in Chagas disease.

Dataset Information

MiR-146b-5p has a sex-specific role in renal and cardiac pathology in a rat model of chronic kidney disease.

Publications

miR-146b-5p has a sex-specific role in renal and cardiac pathology in a rat model of chronic kidney disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets