Yan Dai1, Zhang Mao1, Xu Han1, Youwei Xu1, Lina Xu1, Lianhong Yin1, Yan Qi1, Jinyong Peng1,2,3. 1. College of Pharmacy, Dalian Medical University, Dalian, China. 2. Key Laboratory for Basic and Applied Research on Pharmacodynamic Substances of Traditional Chinese Medicine of Liaoning Province, Dalian Medical University, Dalian, China. 3. National-Local Joint Engineering Research Center for Drug Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian, China.
Abstract
BACKGROUND AND PURPOSE: The microRNA miR-29b-3p shows important roles in regulating apoptosis and inflammation. However, its effects on intestinal ischaemia/reperfusion (II/R) injury have not been reported. Here we have investigated the functions of miR-29b-3p on II/R injury on order to find drug targets to treat the injury. EXPERIMENTAL APPROACH: Two models - in vitro hypoxia/reoxygenation (H/R) of IEC-6 cells; in vivo, II/R injury in C57BL/6 mice were used. Western blotting and dual-luciferase reporter assays were used and mimic and siRNA transfection tests were applied to assess the effects of miR-29b-3p on II/R injury via targeting TNF receptor-associated factor 3 (TRAF3). KEY RESULTS: The H/R procedure decreased cell viability and promoted inflammation and apoptosis in IEC-6 cells, and the II/R procedure also promoted intestinal inflammation and apoptosis in mice. Expression levels of miR-29b-3p were decreased in H/R-induced cells and II/R-induced intestinal tissues of mice compared with control group or sham group, which directly targeted TRAF3. Decreased miR-29b-3p level markedly increased TRAF3 expression via activating TGF-α-activated kinase 1 phosphorylation, increasing NF-κB (p65) levels to promote inflammation, up-regulating Bcl2-associated X expression, and down-regulating Bcl-2 expression to trigger apoptosis. In addition, the miR-29b-3p mimetic and TRAF3 siRNA in IEC-6 cells markedly suppressed apoptosis and inflammation to alleviate II/R injury via inhibiting TRAF3 signallimg. CONCLUSIONS AND IMPLICATIONS: The miR-29b-3p played a critical role in II/R injury, via targeting TRAF3, which should be considered as a significant drug target to treat the disease.
BACKGROUND AND PURPOSE: The microRNA miR-29b-3p shows important roles in regulating apoptosis and inflammation. However, its effects on intestinal ischaemia/reperfusion (II/R) injury have not been reported. Here we have investigated the functions of miR-29b-3p on II/R injury on order to find drug targets to treat the injury. EXPERIMENTAL APPROACH: Two models - in vitro hypoxia/reoxygenation (H/R) of IEC-6 cells; in vivo, II/R injury in C57BL/6 mice were used. Western blotting and dual-luciferase reporter assays were used and mimic and siRNA transfection tests were applied to assess the effects of miR-29b-3p on II/R injury via targeting TNF receptor-associated factor 3 (TRAF3). KEY RESULTS: The H/R procedure decreased cell viability and promoted inflammation and apoptosis in IEC-6 cells, and the II/R procedure also promoted intestinal inflammation and apoptosis in mice. Expression levels of miR-29b-3p were decreased in H/R-induced cells and II/R-induced intestinal tissues of mice compared with control group or sham group, which directly targeted TRAF3. Decreased miR-29b-3p level markedly increased TRAF3 expression via activating TGF-α-activated kinase 1 phosphorylation, increasing NF-κB (p65) levels to promote inflammation, up-regulating Bcl2-associated X expression, and down-regulating Bcl-2 expression to trigger apoptosis. In addition, the miR-29b-3p mimetic and TRAF3 siRNA in IEC-6 cells markedly suppressed apoptosis and inflammation to alleviate II/R injury via inhibiting TRAF3 signallimg. CONCLUSIONS AND IMPLICATIONS: The miR-29b-3p played a critical role in II/R injury, via targeting TRAF3, which should be considered as a significant drug target to treat the disease.
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