MicroRNA-21 (miR-21) contributes to the pathogenesis of fibrogenic diseases in multiple organs, including the kidneys. Highly specific oligonucleotides that distribute to the kidney and inhibit miR-21 function when administered subcutaneously have been recently developed. In a murine model of Alport nephropathy, miR-21 silencing resulted in milder kidney disease, with minimal albuminuria and dysfunction. miR-21 silencing dramatically improved survival of Alport mice and reduced glomerulosclerosis, interstitial fibrosis, tubular injury, and inflammation. Anti–miR-21 enhanced PPAR?/retinoid X receptor (PPAR?/RXR) activity and downstream signaling pathways in glomerular, tubular, and interstitial cells. Inhibition of miR-21 was protective against TGF-?–induced fibrogenesis and inflammation in glomerular and interstitial cells, likely as the result of enhanced PPAR?/RXR activity and improved mitochondrial function. In summary, inhibition of miR-21 is a potential therapeutic strategy for chronic kidney diseases including Alport nephropathy.
Posted by Nicola Brunetti-Pierri