Small Interfering RNA Targeting TNF-α Gene Significantly Attenuates Renal Ischemia-Reperfusion Injury in Mice

Tumor necrosis factor-alpha（TNF-α） has been found to be centrally involved in the development of ischemia-reperfusion injury（IRI）-induced inflammation and apoptosis. Knockdown of TNF-α gene using small interfering RNA（si RNA） may protect renal IRI. Renal IRI was induced in mice by clamping the left renal pedicle for 25 or 35 min. TNF-α si RNA was administered intravenously to silence the expression of TNF-α. The therapeutic effects of si RNA were evaluated in terms of renal function, histological examination, and overall survival following lethal IRI. A single systemic injection of TNF-α si RNA resulted in significant knockdown of TNF-α expression in ischemia-reperfusion injured kidney. In comparison with control mice, levels of BUN and serum creatinine were significantly reduced in mice treated with si RNA. Pathological examination demonstrated that tissue damage caused by IRI was markedly reduced as a result of TNF-α si RNA treatment. Furthermore, survival experiments showed that nearly 90% of control mice died from lethal IRI, whereas more than 50% of si RNApretreated mice survived until the end of the eight-day observation period. We have demonstrated for the first time that silencing TNF-α by specific si RNA can significantly reduce renal IRI and protect mice against lethal kidney ischemia, highlighting the potential for si RNA-based clinical therapy.

miR-148b-3p promotes migration of Schwann cells by targeting cullin-associated and neddylationdissociated 1

MicroRNAs（miRNAs） are small,non-coding RNAs that negatively adjust gene expression in multifarious biological processes.However,the regulatory effects of miRNAs on Schwann cells remain poorly understood.Previous microarray analysis results have shown that miRNA expression is altered following sciatic nerve transaction,thereby affecting proliferation and migration of Schwann cells.This study investigated whether miR-148b-3p could regulate migration of Schwann cells by directly targeting cullin-associated and neddylation-dissociated 1（Cand1）.Up-regulated expression of miR-148b-3p promoted Schwann cell migration,whereas silencing of miR-148b-3p inhibited Schwann cell migration in vitro.Further experiments confirmed that Candl was a direct target of miR-148b-3p,and Candl knockdown reversed suppression of the miR-148b-3p inhibitor on Schwann cell migration.These results suggested that miR-148b-3p promoted migration of Schwann cells by directly targeting Candl in vitro.