biostudies-literatureShi Xthe 111 ProjectScience and Technology Innovation Plan-Basic Research ProjectsChinese Academy of Medical SciencesNational Science Foundation of ChinaNational Natural Science Foundation of Chinathe Shanghai Municipal Science and Technology Major Projecte711https://www.ebi.ac.uk/biostudies/studies/S-EPMC8792399biostudies-literatureUnknown12(1)Treatments for pulmonary fibrosis (PF) are ineffective because its molecular pathogenesis and therapeutic targets are unclear. Here, we show that the expression of low-density lipoprotein receptor (LDLR) was significantly decreased in alveolar type II (ATII) and fibroblast cells, whereas it was increased in endothelial cells from systemic sclerosis-related PF (SSc-PF) patients and idiopathic PF (IPF) patients compared with healthy controls. However, the plasma levels of low-density lipoprotein (LDL) increased in SSc-PF and IPF patients. The disrupted LDL-LDLR metabolism was also observed in four mouse PF models. Upon bleomycin (BLM) treatment, Ldlr-deficient (Ldlr-/-) mice exhibited remarkably higher LDL levels, abundant apoptosis, increased fibroblast-like endothelial and ATII cells and sClinical and translational medicineLDLR dysfunction induces LDL accumulation and promotes pulmonary fibrosis.PMC8792399819032038177006620JC14173002017SHZDZX012019‐I2M‐5‐066315210032019-I2M-5-066B130168203000633Zou HLiu JMei XZuo XLiu QMa YJiang SZhang RGao FWang JShi XZhao YWang LKe YSong NXia JWang QZhao SGuo GSun DChen YWu WTang YJin LYin WYang LChen JWei DCui JZhu HXu JLi YHuang YDistler JHWPu WLuo RXu WTu WDai HfalseLDLR dysfunction induces LDL accumulation and promotes pulmonary fibrosis.Treatments for pulmonary fibrosis (PF) are ineffective because its molecular pathogenesis and therapeutic targets are unclear. Here, we show that the expression of low-density lipoprotein receptor (LDLR) was significantly decreased in alveolar type II (ATII) and fibroblast cells, whereas it was increased in endothelial cells from systemic sclerosis-related PF (SSc-PF) patients and idiopathic PF (IPF) patients compared with healthy controls. However, the plasma levels of low-density lipoprotein (LDL) increased in SSc-PF and IPF patients. The disrupted LDL-LDLR metabolism was also observed in four mouse PF models. Upon bleomycin (BLM) treatment, Ldlr-deficient (Ldlr-/-) mice exhibited remarkably higher LDL levels, abundant apoptosis, increased fibroblast-like endothelial and ATII cells and s2022-01-01T00:00:00Z2022 Jan2026-07-16T18:44:40.96Z2025-04-05T11:18:23.182ZS-EPMC87923993508388110.1002/ctm2.711