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Hyaluronidase2 (Hyal2) modulates low shear stress‐induced glycocalyx impairment via the LKB1/AMPK/NADPH oxidase‐dependent pathway

机译:Hyaluronidase2 (Hyal2)调节低剪切应力诱导glycocalyx障碍通过LKB1 AMPK / NADPH氧化酶相关的通路

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摘要

The endothelium glycocalyx layer (ECL), presents on the apical surface of endothelial cells, creates a barrier between circulating blood and the vessel wall. Low shear stress (LSS) may accelerate the degradation of the glycocalyx via hyaluronidase2 (Hyal2) and then alter the cell polarity. Yet the liver kinase B1 (LKB1) signaling pathway plays an important role in regulating cell polarity. However, the relationship between LKB1 and glycocalyx during LSS is not clear. In the current study, we demonstrate that LSS attenuates LKB1 and AMP‐activated protein kinase activation as well as activated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p47 phox ) and Hyal2 in the human umbilical vein endothelial cell (HUVEC). Pretreatment with 5‐Aminoimidazole‐4‐carboxamide1‐β‐D‐ribofuranoside?(AICAR), or diphenyleneiodonium?(DPI chloride) and transfection with LKB1 overexpression vector and p47 phox small interfering RNA downregulated LSS‐induced Hyal2 activation. By coimmunoprecipitation, we discovered the existence of p47 phox /Hyal2 complex. LSS induced the dissociation of p47 phox /Hyal2 complex, which was inhibited by LKB1 overexpression and AICAR. Furthermore, knockdown of Hyal2 performed a positive feedback on LKB1 activity. In addition, we also show that LSS enhanced LKB1 translocation from the cytosol to the nucleus. Taken together, these data indicate that Hyal2 regulates LSS‐induced injury of the glycocalyx via LKB1/AMPK/NADPH oxidase signaling cascades.
机译:内皮glycocalyx层(ECL),礼物在内皮细胞表面的顶端,创建一个循环血液和之间的屏障血管壁。加快glycocalyx通过退化hyaluronidase2 (Hyal2),然后改变细胞极性。信号通路中发挥着重要作用调节细胞的极性。LKB1和glycocalyx之间的关系LSS还不清楚。证明LSS变弱LKB1和AMP激活的蛋白激酶激活应承担的烟酰胺腺嘌呤二核苷酸作为激活磷酸(NADPH)氧化酶(p47 phox)和Hyal2在人脐静脉内皮细胞(HUVEC)。

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