Down-regulated miR-448 relieves spinal cord ischemia/reperfusion injury by up-regulating SIRT1

Abstract

MicroRNAs play a crucial role in the progression of spinal cord ischemia/reperfusion injury (SCII). The role of miR-448 and SIRT1 in SCII was investigated in this study, to provide further insights into prevention and improvement of this disorder. In this study, expressions of miR-448 and SIRT1 protein were determined by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze cell apoptosis. The endogenous expression of genes was modulated by recombinant plasmids and cell transfection. Dual-luciferase reporter assay was performed to determine the interaction between miR-448 and SIRT1. The Basso, Beattie, and Bresnahan score was used to measure the hind-limb function of rat. The spinal cord ischemia reperfusion injury model of adult rats was developed by abdominal aorta clamping, and the nerve function evaluation was completed by motor deficit index score. In SCII tissues and cells treated with hypoxia, miR-448 was up-regulated while SIRT1 was down-regulated. Hypoxia treatment reduced the expression of SIRT1 through up-regulating miR-448 in nerve cells. Up-regulation of miR-448 induced by hypoxia promoted apoptosis of nerve cells through down-regulating SIRT1. Down-regulated miR-448 improved neurological function and hind-limb motor function of rats with SCII by up-regulating SIRT1. Down-regulated miR-448 inhibited apoptosis of nerve cells and improved neurological function by up-regulating SIRT1, which contributes to relieving SCII.

Suppression of TLR4 by miR-448 is involved in Diabetic development via regulating Macrophage polarization

“…Another important finding of this study was that miR‐448 was critically related to the LPS‐induced M1 polarization of macrophages. As small, non‐protein coding RNA, miR‐448 played an essential role in cellular functions, including proliferation, migration, and apoptosis through regulating the expression of targeted mRNAs . MiR‐448 was recently found to reduce in peripheral blood of T2D patients after laparoscopic bariatric surgery and overexpressed miR‐448 suppressed the viability and invasion of circulating endothelial progenitor cells through targeting SIRT1 .…”

“…As small, non-protein coding RNA, miR-448 played an essential role in cellular functions, including proliferation, migration, and apoptosis through regulating the expression of targeted mRNAs. [34,35] MiR-448 was recently found to reduce in peripheral blood of T2D patients after laparoscopic bariatric surgery and overexpressed miR-448 suppressed the viability and invasion of circulating endothelial progenitor cells through targeting SIRT1. [36] In contrast to TLR4, our data showed that miR-448 was significantly decreased in T2D mice-derived macrophages.…”

Quantitative proteomics reveal the alterations in the spinal�cord after myocardial ischemia‑reperfusion injury in rats

“…The present study attempted to systematically profile the proteome-wide alterations of the spinal cord after myocardial IR injury by quantitative proteomics and further analyzed the possible regulatory mechanisms among the various pathways, and protein-interaction networks. The myocardial IR injury rat model first established by cross clamping the LAD for 30-min ischemia and followed by reperfusion for 2 h, as reported previously (47,48), which showed a significant histopathological and functional myocardial injury. Then using the stable isotope dimethyl labeling quantitative proteomics strategy, a total of 2,362 shared proteins with a good distribution and correlation were successfully quantified.…”

The transcription factor Foxd3 induces spinal cord ischemia-reperfusion injury by potentiating microRNA-214-dependent inhibition of Kcnk2

“…The motor function of the hind limbs was assessed 7 days after surgery using the Basso, Beattie, and Bresnahan (BBB) motor rating scale, based on the motor capacity of the SCII rats. The BBB score ranged from 0 to 21, with 0 indicating no locomotion and 21 indicating normal motor function 23,24 . The score was determined by two independent observers who had not performed the experiment, and the scores of the two observers were averaged.…”