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Hyaluronidase2 (Hyal2) modulates low shear stress‐induced glycocalyx impairment via the LKB1/AMPK/NADPH oxidase‐dependent pathway
Author(s) -
Yang Hongfeng,
Zhu Linlin,
Chao Yuelin,
Gu Yue,
Kong Xiangquan,
Chen Mingxing,
Ye Peng,
Luo Jie,
Chen Shaoliang
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26944
Subject(s) - glycocalyx , ampk , microbiology and biotechnology , nicotinamide adenine dinucleotide phosphate , small interfering rna , nadph oxidase , cell polarity , chemistry , protein kinase a , signal transduction , transfection , kinase , biology , cell , oxidase test , biochemistry , enzyme , reactive oxygen species , gene
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.