Effect of Short Term Exercise and High Fat Diet on Skeletal Muscle miR133a

Micro RNAs (miR) are small non-coding RNA that regulate gene expression at the post-transcriptional level. miR133a is abundant in cardiac and skeletal muscle. In skeletal muscle, miR133a is best known for its regulatory role in myogenesis and differentiation. Nie (2016) found that muscle miR133a expression increased after acute exercise and with 12w of treadmill exercise training in mice. Knockdown of miR133a in transgenic mice resulted in blunted skeletal muscle mitochondrial biogenesis and function in response to exercise training (Nie, 2016) suggesting a role for miR133a in regulating the normal skeletal muscle metabolic adaptive response to exercise. Among other miR, skeletal muscle miR133a is reported as downregulated in insulin-resistant muscle. Insulin resistance in mice fed a high-fat diet is detectable after 3 days on diet (Lee, 2011). In this study, voluntary, rather than forced, exercise was employed to test whether miR133a expression is regulated early in the adoption of increased daily physical activity

Hypoxia-induced long non-coding RNA Malat1 is dispensable for renal ischemia/reperfusion-injury

Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury (AKI). Non-coding RNAs are crucially involved in its pathophysiology. We identified hypoxia-induced long non-coding RNA Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) to be upregulated in renal I/R injury. We here elucidated the functional role of Malat1 in vitro and its potential contribution to kidney injury in vivo. Malat1 was upregulated in kidney biopsies and plasma of patients with AKI, in murine hypoxic kidney tissue as well as in cultured and ex vivo sorted hypoxic endothelial cells and tubular epithelial cells. Malat1 was transcriptionally activated by hypoxia-inducible factor 1-a. In vitro, Malat1 inhibition reduced proliferation and the number of endothelial cells in the S-phase of the cell cycle. In vivo, Malat1 knockout and wildtype mice showed similar degrees of outer medullary tubular epithelial injury, proliferation, capillary rarefaction, inflammation and fibrosis, survival and kidney function. Small-RNA sequencing and whole genome expression analysis revealed only minor changes between ischemic Malat1 knockout and wildtype mice. Contrary to previous studies, which suggested a prominent role of Malat1 in the induction of disease, we did not confirm an in vivo role of Malat1 concerning renal I/Rinjury