ArticleInternational journal of molecular sciences2023
LRG1 Promotes ECM Integrity by Activating the TGF-β Signaling Pathway in Fibroblasts.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 23 citations in OpenAlex.
- Skin Aging: From Molecular Mechanisms to Therapeutic and Technological Innovations.Journal of cellular and molecular medicine · 2026Review
- The Role of the Notch1 Signaling Pathway in the Pathogenesis and Treatment of Diabetic Foot: A Review.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2026Review
- Placenta-Derived Extracellular Vesicles (pdEVs): Key Mediators That Affect the Metabolic Health of Offspring in Early Nutritional Environments.Biomolecules · 2026Review
- LRG1 as a Potential Therapeutic Target in Atherosclerosis: Mechanistic Basis and Current Evidence.Cells · 2026Review
- Mitochondrial mGPDH Modulates Fibroblast Function in Diabetic Wound Healing via the SIRT1-c-Myc-TGF-β1 Axis.Diabetes · 2026Article
- Do LRG1-SERPINA1 Interactions Modulate Fibrotic and Inflammatory Signatures in Rheumatoid Arthritis? A Proteomic and In Silico Investigation.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Article
- Revealing the multiple faces of LRG1: gene expression, structure, function, and therapeutic potential.Journal of advanced research · 2026Review
- Skeletal muscle dysfunction induced by cancer immunotherapy: mechanistics insights and surgical implications.Frontiers in immunology · 2026Review
- Role ofFood chemistry. Molecular sciences · 2025Article
- The critical role of LRG1 in pathological fibrosis.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Role of Growth Factors in the Pathogenesis of Systemic-Sclerosis-Associated Fibrosis.International journal of molecular sciences · 2025Review
- Single-cell transcriptomic landscape of sciatic nerve after transection injury.Journal of neuroinflammation · 2025Article
- Cave adaptation favors aging resilience in the Mexican tetra.npj metabolic health and disease · 2025Article
- Embryonic macrophages orchestrate niche cell homeostasis for the establishment of the definitive hematopoietic stem cell pool.Nature communications · 2025Article
- TGF-β1 induces ROS to activate ferroptosis via the ERK1/2-WISP1 pathway to promote the progression of renal tubular epithelial cell fibrosis.Cytotechnology · 2025Article
- The Function of the TGFβ Signaling Pathway in Connective Tissue Diseases: From Biology to Clinical Application.Journal of inflammation research · 2025Review
- Recent advances in dermal fibroblast senescence and skin aging: unraveling mechanisms and pioneering therapeutic strategies.Frontiers in pharmacology · 2025Review
- Human Hair Follicle Mesenchymal Stem Cell-Derived Exosomes Attenuate UVB-Induced Photoaging via the miR-125b-5p/TGF-β1/Smad Axis.Biomaterials research · 2025Article
- Matrix Metalloproteinases on Skin Photoaging.Journal of cosmetic dermatology · 2024Review
- Integrated approach to reducing polypharmacy in older people: exploring the role of oxidative stress and antioxidant potential therapy.Redox report : communications in free radical research · 2024Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Leucine-rich alpha-2-glycoprotein 1 (LRG1) mediates skin repair and fibrosis by stimulating the transforming growth factor-beta (TGF-β) signaling pathway. In the present study, we investigated the effect of LRG1 on extracellular matrix (ECM) integrity in fibroblasts, as well as on skin aging. The treatment of dermal fibroblasts with purified recombinant human LRG1 increased type I collagen secretion and decreased matrix metalloproteinase-1 secretion. Additionally, LRG1 promoted SMAD2/SMAD3 phosphorylation in a pattern similar to that of TGF-β1 treatment. An inhibitor of TGF-β receptor 1 abolished LRG1-induced SMAD2 phosphorylation. RNA sequencing identified "extracellular region", "extracellular space", and "extracellular matrix" as the main Gene Ontology terms in the differentially expressed genes of fibroblasts treated with or without LRG1. LRG1 increased TGF-β1 mRNA levels, suggesting that LRG1 partially transactivates the expression of TGF-β1. Furthermore, an increased expression of type I collagen was also observed in fibroblasts grown in three-dimensional cultures on a collagen gel mimicking the dermis. LRG1 mRNA and protein levels were significantly reduced in elderly human skin tissues with weakened ECM integrity compared to in young human skin tissues. Taken together, our results suggest that LRG1 could retard skin aging by activating the TGF-β signaling pathway, increasing ECM deposition while decreasing its degradation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.