Monocyte adhesive hyaluronan matrix induced by hyperglycemia in diabetic lung injuries.

Monocyte adhesive hyaluronan matrix induced by hyperglycemia in diabetic lung injuries.
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DOI:
10.1016/j.jbc.2023.104995
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发表时间:
2023-08
影响因子:
4.8
通讯作者:
Hascall, Vincent C.
Hascall, Vincent C.
中科院分区:
生物学2区
文献类型:
--
作者:
Wang, Andrew Jun;Ren, Juan;Wang, Aimin;Hascall, Vincent C.

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炎症前单核细胞和巨噬细胞浸润在糖尿病肺损伤中起重要作用,但其介导机制尚不清楚。在这里,我们表明,气道平滑肌细胞(SMC)激活单核细胞粘附反应高血糖葡萄糖(25.6 mM)显着增加透明质酸(HA)在细胞基质中,与U937单核细胞白血病细胞的粘附同时增加2至4倍。基于HA的结构直接归因于高糖而不是细胞外渗透压的增加,并且它们需要血清对SMC的生长刺激。在高糖环境下用肝素处理SMC诱导合成更大的HA基质,这与我们在肾小球SMC中的观察结果一致。此外,我们观察到增加肿瘤坏死因子刺激基因-6(TSG-6)的表达在高葡萄糖和高葡萄糖加肝素培养,和重链(HC)修饰的HA结构存在于高葡萄糖和高葡萄糖加肝素处理的SMC培养的单核细胞粘附电缆结构。有趣的是,这些HC改性的HA结构沿HA缆线沿着不均匀地分布。此外,重组人TSG-6和HA14寡核苷酸的体外试验表明,肝素对TSG-6诱导的HC转移至HA没有抑制活性,与SMC培养物的结果一致。这些结果支持以下假设:气道平滑肌中的高血糖诱导HA基质的合成,该HA基质募集炎性细胞并建立导致糖尿病肺损伤的慢性炎症过程和纤维化。
Infiltrated pre-inflammatory monocytes and macrophages have important roles in the induction of diabetic lung injuries, but the mechanism mediating their infiltration is still unclear. Here, we showed that airway smooth muscle cells (SMCs) activated monocyte adhesion in response to hyperglycemic glucose (25.6 mM) by significantly increasing hyaluronan (HA) in the cell matrix, with concurrent 2- to 4-fold increases in adhesion of U937 monocytic-leukemic cells. The HA-based structures were attributed directly to the high-glucose and not to increased extracellular osmolality, and they required growth stimulation of SMCs by serum. Treatment of SMCs with heparin in high-glucose induces synthesis of a much larger HA matrix, consistent with our observations in the glomerular SMCs. Further, we observed increases in tumor necrosis factor-stimulated gene-6 (TSG-6) expression in high-glucose and high-glucose plus heparin cultures, and the heavy chain (HC)-modified HA structures existed on the monocyte-adhesive cable structures in high-glucose and in high-glucose plus heparin-treated SMC cultures. Interestingly, these HC-modified HA structures were unevenly distributed along the HA cables. Further, the in vitro assay with recombinant human TSG-6 and the HA14 oligo showed that heparin has no inhibitory activity on the TSG-6-induced HC-transfer to HA, consistent with the results from SMC cultures. These results support the hypothesis that hyperglycemia in airway smooth muscle induces the synthesis of a HA matrix that recruits inflammatory cells and establishes a chronic inflammatory process and fibrosis that lead to diabetic lung injuries.
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