ArticleClinical and translational medicine2022
LDLR dysfunction induces LDL accumulation and promotes pulmonary fibrosis.
Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Advances in metabolic reprogramming of pulmonary fibrosis.Chinese medical journal pulmonary and critical care medicine · 2026Review
- SYISL promotes pulmonary epithelial-mesenchymal transition and fibrosis through DSP-Hippo/YAP pathway.Cellular and molecular life sciences : CMLS · 2026Article
- Epigenome-wide Mendelian randomization with multi-omics validation identifies epigenetic drivers of idiopathic pulmonary fibrosis.Communications biology · 2026Article
- Review
- Transferrin receptor serves a role in promoting PANoptosis in thyroid cancer.Oncology letters · 2026Article
- Xiaoke Decoction Inhibits COX-2-Mediated LDLr Pathway Dysfunction and Protects Renal Function in Diabetic Nephropathy Rats.Current medical science · 2025Article
- Article
- Hsa_circ_0026782 Acts as a "Molecular Break" of CREB1-Mediated Transcription by Promoting Its Phosphorylation at Ser142 That Prevents Keloid Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Machine learning identifies lipid-associated genes and constructs diagnostic and prognostic models for idiopathic pulmonary fibrosis.Orphanet journal of rare diseases · 2025Article
- PCSK9 Enhances Cardiac Fibrogenesis via the Activation of Toll-like Receptor and NLRP3 Inflammasome Signaling.International journal of molecular sciences · 2025Article
- Targeting alveolar epithelial cell metabolism in pulmonary fibrosis: Pioneering an emerging therapeutic strategy.Frontiers in cell and developmental biology · 2025Review
- Aberrant lipid profiles and lymphocyte counts in systemic sclerosis population, reassessing predictive value for concurrent cardiovascular diseases.Frontiers in immunology · 2025Article
- Genetic association of lipids and lipid lowering drug target genes with sarcoidosis.Scientific reports · 2024Article
- Reduced circulating CD63Cardiovascular diabetology · 2024Article
- The novel molecular mechanism of pulmonary fibrosis: insight into lipid metabolism from reanalysis of single-cell RNA-seq databases.Lipids in health and disease · 2024Review
- PCSK9 inhibitor alleviates experimental pulmonary fibrosis-induced pulmonary hypertension via attenuating epithelial-mesenchymal transition by suppressing Wnt/β-catenin signalingFrontiers in medicine · 2024Article
- Glycolysis Reprogramming in Idiopathic Pulmonary Fibrosis: Unveiling the Mystery of Lactate in the Lung.International journal of molecular sciences · 2023Review
- Lipid metabolism in idiopathic pulmonary fibrosis: From pathogenesis to therapy.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Review
- Oxidative Stress and Lipid Accumulation Augments Cell Death in LDLR-Deficient RPE Cells andCells · 2022Article
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Authors and funding
40 authors at 11 institutions in 3 countries.
Funding
Abstract
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 significantly earlier and more severe fibrotic response compared to wild-type mice. In vitro experiments revealed that apoptosis and TGF-β1 production were induced by LDL, while fibroblast-like cell accumulation and ET-1 expression were induced by LDLR knockdown. Treatment of fibroblasts with LDL or culture medium derived from LDL-pretreated endothelial or epithelial cells led to obvious fibrotic responses in vitro. Similar results were observed after LDLR knockdown operation. These results suggest that disturbed LDL-LDLR metabolism contributes in various ways to the malfunction of endothelial and epithelial cells, and fibroblasts during pulmonary fibrogenesis. In addition, pharmacological restoration of LDLR levels by using a combination of atorvastatin and alirocumab inhibited BLM-induced LDL elevation, apoptosis, fibroblast-like cell accumulation and mitigated PF in mice. Therefore, LDL-LDLR may serve as an important mediator in PF, and LDLR enhancing strategies may have beneficial effects on PF.
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