当前位置: X-MOL 学术Egypt. J. Bronchol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Dynamic role of LMW-hyaluronan fragments and Toll-like receptors 2,4 in progression of bleomycin induced lung parenchymal injury to fibrosis
The Egyptian Journal of Bronchology ( IF 1.0 ) Pub Date : 2021-05-21 , DOI: 10.1186/s43168-021-00073-y
Apoorva Pandey , Ritu Kulshrestha , Surendra Kumar Bansal

Pulmonary fibrosis (PF) is a progressive and lethal lung disease of elderly whose incidence has been increasing following the Covid-19 pandemic caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). PF immunopathogenesis involves progressive alveolar epithelial cell damage, release of damage-associated molecular patterns (DAMPs), and extracellular matrix (ECM) injury. We assessed the dynamic role of LMW-hyaluronan (LMW-HA) as DAMP in initiation of host immune TLR-2,4 responses and as determinant in progression of ECM injury to fibrosis. Male Wistar rats were divided into Group I (saline control, n = 24) and Group II (intratracheal bleomycin, 7 U/kg/animal, n = 24). Animals were euthanized on 0, 7, 14, and 28 days. The time course of release of LMW-HA, TLR-2,4 mRNA and protein levels, and NF-κB-p65 levels after bleomycin injury were correlated with the development of parenchymal inflammation, remodelling, and fibrosis. Acute lung injury caused by bleomycin significantly increases the pro-inflammatory LMW-HA levels and elevates TLR-2,4 levels on day 7. Subsequently, TLR-2 upregulation, TLR-4 downregulation, and NF-κB signalling follow on days 14 and 28. This results in progressive tissue inflammation, alveolar and interstitial macrophage accumulation, and fibrosis. LMW-HA significantly increases in PF caused by non-infectious and infectious (Covid-19) etiologies. The accumulating HA fragments function as endogenous DAMPs and trigger inflammatory responses, through differential TLR2 and TLR4 signalling, thus promoting inflammation and macrophage influx. LMW-HA are reflective of the state of ongoing tissue inflammation and may be considered as a natural biosensor for fibrotic lung diseases and as potential therapeutic targets.

中文翻译:

LMW-透明质酸片段和Toll样受体2,4在博来霉素诱导的肺实质性纤维化损伤进展中的动态作用

肺纤维化(PF)是一种老年人的进行性致死性肺部疾病,在严重的急性呼吸系统综合症冠状病毒2(SARS-CoV-2)导致Covid-19大流行之后,其发病率一直在增加。PF免疫发病机制包括进行性肺泡上皮细胞损伤,损伤相关分子模式(DAMP)释放和细胞外基质(ECM)损伤。我们评估了LMW-透明质酸(LMW-HA)作为DAMP在宿主免疫TLR-2,4应答的启动中的动态作用以及在ECM纤维化损伤进展中的决定性作用。将雄性Wistar大鼠分为I组(盐水对照,n = 24)和II组(气管内博来霉素,7U / kg /动物,n = 24)。在第0、7、14和28天对动物实施安乐死。LMW-HA,TLR-2,4 mRNA和蛋白质水平释放的时间过程,博来霉素损伤后的NF-κB-p65和NF-κB-p65水平与实质炎症,重塑和纤维化的发展有关。博来霉素引起的急性肺损伤在第7天显着增加了促炎性LMW-HA的水平,并升高了TLR-2,4的水平。随后,在第14天和之后出现了TLR-2上调,TLR-4下调和NF-κB信号传导。 28.这导致进行性组织炎症,肺泡和间质巨噬细胞蓄积以及纤维化。由非感染性和感染性(Covid-19)病因引起的LMW-HA PF显着增加。积累的HA片段起内源性DAMP的作用,并通过不同的TLR2和TLR4信号转导触发炎症反应,从而促进炎症和巨噬细胞流入。
更新日期:2021-05-22
down
wechat
bug