Department of Emergency, Changzhou City No.1 People's Hospital, Changzhou, Jiangsu Province, 213000, China.
Department of Emergency, Changzhou City No.1 People's Hospital, Changzhou, Jiangsu Province, 213000, China
Biosci Rep. 2019 Mar 1;39(3). doi: 10.1042/BSR20182221. Print 2019 Mar 29.
Acute pancreatitis is a life-threatening disease accompanied by systemic inflammatory response. NF-κB and p38 signal pathways are activated in AP induced by cerulein. And PAKs are multifunctional effectors of Rho GTPases with kinase activity. In the present study, the function of P21-activated kinase 1 (PAK1) in AP was investigated, and found that PAK1 was up-regulated in pancreas of AP mice model, and led to NF-κB and p38 pathway activation. PAK1 inhibition by shRNA or small molecule inhibitor FRAX597 decreased NF-κB and p38 activity, also alleviated the pathological damage in the pancreas of AP mice model, including decreasing the amylase and lipase levels in serum, decreasing the levels of tumor necrosis factor-α, interleukin-6, and interleukin-1β in AP. These results suggested that PAK1 inhibition protects against AP by inhibiting NF-κB and p38 pathways, and indicated that PAK1 is a potential therapy to alleviate AP patients in clinic, and these need to be explored further.
急性胰腺炎是一种危及生命的疾病，伴有全身炎症反应。胆酸钠诱导的胰腺炎中 NF-κB 和 p38 信号通路被激活。PAKs 是 Rho GTPases 的多功能效应物，具有激酶活性。在本研究中，研究了 P21 激活激酶 1（PAK1）在急性胰腺炎中的作用，发现 PAK1 在急性胰腺炎小鼠模型的胰腺中上调，并导致 NF-κB 和 p38 途径的激活。通过 shRNA 或小分子抑制剂 FRAX597 抑制 PAK1 可降低 NF-κB 和 p38 的活性，也可减轻急性胰腺炎小鼠模型的胰腺病理损伤，包括降低血清中淀粉酶和脂肪酶的水平，降低肿瘤坏死因子-α、白细胞介素-6 和白细胞介素-1β 的水平。这些结果表明，PAK1 抑制通过抑制 NF-κB 和 p38 途径来保护急性胰腺炎，表明 PAK1 是一种有潜力的治疗方法，可以减轻临床急性胰腺炎患者的症状，这需要进一步探索。
