Systemic Inhibition of miR-451 Increases Fibrotic Signaling and Diminishes Autophagic Response to Exacerbate Renal Damage in Tallyho/Jng Mice.

Systemic Inhibition of miR-451 Increases Fibrotic Signaling and Diminishes Autophagic Response to Exacerbate Renal Damage in Tallyho/Jng Mice. Am J Physiol Renal Physiol. 2020 Jul 27;: Authors: Fluitt MB, Shivapurkar N, Kumari M, Singh S, Li L, Tiwari S, Ecelbarger CM Abstract MicroRNAs (miRs) provide fine-tuning of gene expression via inhibition of translation. MiR-451 has a modulatory role in cell cycling via down-regulation of the mechanistic target of rapamycin (mTOR). We aimed to test whether chronic, systemic inhibition of miR-451 would enhance renal fibrosis (associated with deranged autophagy). Adult, TallyHo/Jng mice (obese, insulin-resistant) were randomized to two treatment groups to receive either miR-451 inhibition (via a locked nucleic acid, LNA, construct) or a similar scrambled-LNA control for 8 weeks. All mice were fed a high-fat diet (60% kcal from fat) ad libitum and humanely euthanized after 12 weeks. Kidneys and blood were collected for analysis. Renal expression of miR-451 was 6-fold lower in inhibitor-treated mice, compared to control mice. MiR-451 inhibition increased kidney weight, collagen, and glycogen deposition. Blood chemistry revealed significantly higher Na+ and anion gap (relative metabolic acidosis) in inhibitor-treated mice. Western blotting and immunohistochemistry of kidney revealed that the inhibitor increased markers of renal injury and fibrosis, e.g., kidney injury molecule 1 (KIM1) and neutrop...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research