Potential role of ACE2-related microRNAs in COVID-19-associated nephropathy

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for coronavirus disease (COVID-19), potentially have severe kidney adverse effects. This organ expressed angiotensin-converting enzyme 2 (ACE2), the transmembrane protein which facilitate the entering of the virus into the cell. Therefore, early detection of the kidney manifestations of COVID-19 is crucial. Previous studies showed ACE2 role in various indications of this disease, especially in kidney effects. The MicroRNAs (miRNAs) in this organ affected ACE2 expression. Therefore, this review aims at summarizing the literature of a novel miRNA-based therapy and its potential applications in COVID-19-associated nephropathy. Furthermore, previous studies were analyzed for the kidney manifestations of COVID-19 and the miRNAs role that were published on the online databases, namely MEDLINE (PubMed) and Scopus. Several miRNAs, particularly miR-18 (which was upregulated in nephropathy), played a crucial role in ACE2 expression. Therefore, the antimiR-18 roles were summarized in various primate models that aided in developing the therapy for ACE2 related diseases.

Keywords: ACE2; COVID-19; Nephropathy; microRNAs.

Fig. 1

The SARS-CoV-2 infection impact on the podocyte cytoskeletal protein. (A) Normal glomerulus without podocyte, mesangial cell, and parietal epithelial cell impairment. (B) Injured podocyte leads to glomerular sclerosis. (C) Podocyte integrity with normal cytoskeletal proteins expression. (D) Impairment in podocyte integrity, effacement, apoptosis, and collapse, as virus abnormality impact. The virus makes the cytokine-storm and the proinflammatory mediators responsible for podocyte apoptosis, collapse, and effacement, to clinically manifest as AKI and protein-loss.

Fig. 2

Pathological mechanism underlying the kidney manifestations of SARS-CoV-2 involving proinflammatory mediators and miR expression. Several miRNAs involve in ACE2 expression, while most of them are affected in other organs, and miR-18 and -125b are specifically expressed in the kidney. Currently, only antimir-18 has a good evidence-based study as an ACE2 expression silencer.

Fig. 3

The miRNAs potential in kidney disease, a bench to bedside approach (in vitro and in vivo models) are used to screen the most useful miRNAs in ACE2 associated nephropathy. The patient samples are screened using high-throughput techniques. The miRNAs is further used as innovative therapeutic approach to improve kidney function in the ACE2-associated nephropathy patients.