Ablation of LRP6 in alpha-smooth muscle actin-expressing cells abrogates lung inflammation and fibrosis upon bleomycin-induced lung injury

IF 3.5 4区生物学 Q1 Biochemistry, Genetics and Molecular Biology

FEBS Letters Pub Date : 2025-01-28 DOI:10.1002/1873-3468.15106

Eun-Ah Sung, Mikhail G. Dozmorov, SuJeong Song, Theingi Aung, Min Hee Park, Patricia J. Sime, Wook-Jin Chae

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Abstract

Tissue fibrosis is a progressive pathological process with excessive deposition of extracellular matrix proteins (ECM). Myofibroblasts, identified by alpha-smooth muscle actin (αSMA) expression, play an important role in tissue fibrosis by producing ECM. Here, we found that the Wnt antagonist Dickkopf1 (DKK1) induced gene expressions associated with inflammation and fibrosis in lung fibroblasts. We demonstrated that genetic deletion of LRP6, a receptor for Wnt ligands and DKK1, in αSMA-expressing cells using Acta2-cre Lrp6^fl/fl (Lrp6^AKO) mice abrogated the bleomycin (BLM)-induced lung inflammation and fibrosis phenotype, suggesting an important role for LRP6 in modulating inflammation and fibrotic processes in the lung. Our results highlight the crucial role of LRP6 in fibroblasts in regulating inflammation and fibrosis upon BLM-induced lung injury.

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消融α -平滑肌肌动蛋白表达细胞中的LRP6可消除博莱霉素诱导的肺损伤后的肺部炎症和纤维化。

组织纤维化是细胞外基质蛋白（ECM）过度沉积的进行性病理过程。肌成纤维细胞通过α -平滑肌肌动蛋白（αSMA）的表达在组织纤维化中发挥重要作用。在这里，我们发现Wnt拮抗剂Dickkopf1 （DKK1）诱导肺成纤维细胞中与炎症和纤维化相关的基因表达。我们利用Acta2-cre Lrp6fl/fl （Lrp6AKO）小鼠证实，在α sma表达细胞中，基因缺失LRP6 （Wnt配体和DKK1的受体）可消除博来霉素（BLM）诱导的肺部炎症和纤维化表型，表明LRP6在调节肺部炎症和纤维化过程中发挥重要作用。我们的研究结果强调了LRP6在blm诱导的肺损伤中调节成纤维细胞炎症和纤维化的关键作用。

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来源期刊

FEBS Letters 生物-生化与分子生物学

CiteScore

7.00

自引率

2.90%

发文量

303

审稿时长

1.0 months

期刊介绍： FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.