Shi-Wen Cai1, Ying Han1, Guo-Ping Wang2. 1. Intensive Care Unit, Chang An Hospital Xi'an, Shaanxi, China. 2. Emergency Department, Chang An Hospital Xi'an, Shaanxi, China.
Abstract
BACKGROUND: Acute pancreatitis (AP) is a necro-inflammatory disorder with high mortality rate. With advances in understanding the pathogenesis of AP, microRNAs (miRNAs) have been reported to play an essential role in AP progression. However, the mechanism that allows miR-148a-3p to regulate necrosis in AP remains unclear. METHODS: Caerulein treatment was used to induce AP in mice or cells. miR-148a-3p-/- mice or miR-148a-3p inhibition in wild type mice were used to investigate the effect of miR-148a-3p on AP. The expression of miR-148a-3p was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The abundances of phosphatase and tensin homolog (PTEN) and hallmarks of necrosis or apoptosis were measured by qRT-PCR or western blots (WB). Cell necrosis, apoptosis, serum amylase or lipase activity and inflammatory cytokines levels were investigated by commercial assay kit. Inflammatory infiltration was analyzed by immunohistochemistry (IHC). The interaction between miR-148a-3p and PTEN was probed by luciferase activity. RESULTS: miR-148a-3p was highly expressed in AP and knockout of miR-148a-3p inhibited water content, cell necrosis, amylase and lipase activity while inducing PTEN expression. Moreover, miR-148a-3p deletion attenuated inflammatory infiltration and necrosis by promoting apoptosis. In addition, miR-148a-3p knockdown protected against cell necrosis, amylase, and lipase activity in AP. Intriguingly, PTEN was a target of miR-148a-3p and interference of PTEN reversed the effect of miR-148a-3p deficiency on AP in vitro. CONCLUSION: miR-148a-3p inhibition repressed necrosis by regulating PTEN expression in AP, providing a novel biomarker of therapeutics for AP treatment. IJCEP
BACKGROUND: Acute pancreatitis (AP) is a necro-inflammatory disorder with high mortality rate. With advances in understanding the pathogenesis of AP, microRNAs (miRNAs) have been reported to play an essential role in AP progression. However, the mechanism that allows miR-148a-3p to regulate necrosis in AP remains unclear. METHODS: Caerulein treatment was used to induce AP in mice or cells. miR-148a-3p-/- mice or miR-148a-3p inhibition in wild type mice were used to investigate the effect of miR-148a-3p on AP. The expression of miR-148a-3p was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The abundances of phosphatase and tensin homolog (PTEN) and hallmarks of necrosis or apoptosis were measured by qRT-PCR or western blots (WB). Cell necrosis, apoptosis, serum amylase or lipase activity and inflammatory cytokines levels were investigated by commercial assay kit. Inflammatory infiltration was analyzed by immunohistochemistry (IHC). The interaction between miR-148a-3p and PTEN was probed by luciferase activity. RESULTS:miR-148a-3p was highly expressed in AP and knockout of miR-148a-3p inhibited water content, cell necrosis, amylase and lipase activity while inducing PTEN expression. Moreover, miR-148a-3p deletion attenuated inflammatory infiltration and necrosis by promoting apoptosis. In addition, miR-148a-3p knockdown protected against cell necrosis, amylase, and lipase activity in AP. Intriguingly, PTEN was a target of miR-148a-3p and interference of PTEN reversed the effect of miR-148a-3p deficiency on AP in vitro. CONCLUSION:miR-148a-3p inhibition repressed necrosis by regulating PTEN expression in AP, providing a novel biomarker of therapeutics for AP treatment. IJCEP