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LOXL4, but not LOXL2, is the critical determinant of pathological collagen cross-linking and fibrosis in the lung
Science Advances ( IF 13.6 ) Pub Date : 2023-05-26 , DOI: 10.1126/sciadv.adf0133
Hsiao-Yen Ma 1 , Qingling Li 2 , Weng Ruh Wong 2 , Elsa-Noah N'Diaye 1 , Patrick Caplazi 3 , Hannah Bender 3 , Zhiyu Huang 4 , Alexander Arlantico 4 , Surinder Jeet 4 , Aaron Wong 4 , Claire Emson 4 , Hans Brightbill 4 , Lucinda Tam 5 , Robert Newman 5 , Merone Roose-Girma 5 , Wendy Sandoval 2 , Ning Ding 1
Affiliation  

Idiopathic pulmonary fibrosis is a progressive fibrotic disease characterized by excessive deposition of (myo)fibroblast produced collagen fibrils in alveolar areas of the lung. Lysyl oxidases (LOXs) have been proposed to be the central enzymes that catalyze the cross-linking of collagen fibers. Here, we report that, while its expression is increased in fibrotic lungs, genetic ablation of LOXL2 only leads to a modest reduction of pathological collagen cross-linking but not fibrosis in the lung. On the other hand, loss of another LOX family member, LOXL4, markedly disrupts pathological collagen cross-linking and fibrosis in the lung. Furthermore, knockout of both Loxl2 and Loxl4 does not offer any additive antifibrotic effects when compared to Loxl4 deletion only, as LOXL4 deficiency decreases the expression of other LOX family members including Loxl2 . On the basis of these results, we propose that LOXL4 is the main LOX activity underlying pathological collagen cross-linking and lung fibrosis.

中文翻译:

LOXL4,而非 LOXL2,是肺部病理性胶原交联和纤维化的关键决定因素

特发性肺纤维化是一种进行性纤维化疾病,其特征是(肌)成纤维细胞产生的胶原纤维在肺的肺泡区域过度沉积。已提出赖氨酰氧化酶 (LOX) 是催化胶原纤维交联的中心酶。在这里,我们报告说,虽然它在纤维化肺中的表达增加,但 LOXL2 的基因消融只会导致病理性胶原交联适度减少,但不会导致肺纤维化。另一方面,另一个 LOX 家族成员 LOXL4 的缺失会显着破坏肺部的病理性胶原交联和纤维化。此外,两者的淘汰赛Loxl2Loxl4与相比时不提供任何附加的抗纤维化作用Loxl4仅删除,因为 LOXL4 缺陷会降低其他 LOX 家族成员的表达,包括Loxl2. 基于这些结果,我们提出 LOXL4 是病理性胶原交联和肺纤维化的主要 LOX 活性。
更新日期:2023-05-26
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