The Impact of Physical Exercise on microRNAs in Hemodialysis Patients: A Review and a Protocol for an Ancillary Study

Abstract

Physical inactivity is considered a significant risk factor for mortality and morbidity among chronic hemodialysis (HD) patients. Therefore, physical exercise is recommended in the treatment of HD patients. Although the beneficial effects of physical exercise in HD patients are well-described in the literature, the underlying physiological mechanisms still need to be fully understood. Recently, microRNAs (miRNAs) have emerged as potential mediators of the therapeutic effects of physical exercise in healthy individuals. miRNAs are short, single-stranded, noncoding RNAs involved in gene expression regulation. Specifically, upon forming the RNA-induced silencing complex, miRNAs selectively bind to specific miRNAs within cells, reducing gene expression. miRNAs can be secreted by cells in an accessible form or enclosed within exosomes or extracellular vesicles. They can be detected in various body fluids, including serum (circulating miRNAs), facilitating the study of their diverse expression. Currently, there is no available data regarding the impact of physical exercise on the expression of miRNAs involved in osteogenic differentiation, a fundamental mechanism in the development of vascular calcification, for HD patients. Therefore, we have designed an observational and longitudinal case-control study to evaluate the expression of miR-9 and miR-30b in HD patients participating in a 3-month interdialytic physical exercise program. This paper aims to present the study protocol and review the expression of circulating miRNAs in HD patients and their modulation through physical exercise.

Keywords: chondrogenesis; endothelial dysfunction; endothelial progenitor cells; exercise therapy; osteogenesis; physical activity; vascular calcification.

Figure 1

The figure illustrates the biogenesis of microRNAs, which begins with forming primary microRNA transcripts (pri-miRNA) and is subsequently processed by Drosha to generate pre-miRNA. Once exported to the cytoplasm, the Dicer complex is recruited to remove the stem-loop from pre-miRNA, forming mature miRNA. One strand of the miRNA duplex is then incorporated into the RNA-induced silencing complex (RISC). Within the RISC, miRNAs bind to complementary sequences on target mRNAs, leading to the repression of their translation or the induction of their degradation. However, cells can also secrete miRNAs and release them into circulation, contributing to cellular crosstalk and epithelial–mesenchymal transition, angiogenesis, fibrosis, inflammation, and osteogenic differentiation. Specifically, some of the miRNAs whose levels increase following physical activity are highlighted.