ArticleLaboratory investigation; a journal of technical methods and pathology2019
Lysyl oxidase enzymes mediate TGF-β1-induced fibrotic phenotypes in human skin-like tissues.
Article in Laboratory investigation; a journal of technical methods and pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Bibliometric analysis combined with visualization on universal trends and hot topics of LOX family in human diseases: 1995 to 2025.Frontiers in oncology · 2025Pooled it
- LOXL4: a key regulatory factor at the intersection of fibrosis and tumor progression.Human cell · 2026Review
- Integrin-mediated mechanotransduction in the tumor microenvironment: macrophage-centered signaling mechanisms and immune remodeling.Journal of translational medicine · 2026Review
- Inflammation reprograms fibro-adipogenic progenitors to sustain immunopathogenic niches in myositis.Cell death & disease · 2026Article
- Assessing preterm risk via label-free, multiparametric imaging of collagen fiber remodeling in the cervix.Biomedical optics express · 2026Article
- RUNX1 is expressed in a subpopulation of dermal fibroblasts and is associated with disease severity of systemic sclerosis.Annals of the rheumatic diseases · 2026Article
- Submacular tissue repair and fibrosis in neovascular macular degeneration: A predictable outcome secondary to a chronic age-related endotheliopathy.Molecular vision · 2026Review
- A highly potent bi-thiazole inhibitor of LOX rewires collagen architecture and enhances chemoresponse in triple-negative breast cancer.Cell chemical biology · 2024Article
- Cell-type specific effects of mineralocorticoid receptor gene expression suggest intercellular communication regulating fibrosis in skeletal muscle disease.Frontiers in physiology · 2024Article
- Label-free, multi-parametric assessments of cell metabolism and matrix remodeling within human and early-stage murine osteoarthritic articular cartilage.Communications biology · 2023Article
- Extracellular matrix stiffness-The central cue for skin fibrosis.Frontiers in molecular biosciences · 2023Review
- Smurf2 Regulates Inflammation and Collagen Processing in Cutaneous Wound Healing through Transforming Growth Factor-β/Smad3 Signaling.The American journal of pathology · 2022Article
- Self-Assembled Human Skin Equivalents Model Macrophage Activation of Cutaneous Fibrogenesis in Systemic Sclerosis.Arthritis & rheumatology (Hoboken, N.J.) · 2022Article
- Regulators of collagen crosslinking in developing and adult tendons.European cells & materials · 2022Review
- Immune Regulation of Mammary Fibroblasts and the Impact of Mammographic Density.Journal of clinical medicine · 2022Article
- Following historical "tracks" of hair follicle miniaturisation in patterned hair loss: Are elastin bodies the forgotten aetiology?Experimental dermatology · 2022Article
- Substrate stiffness engineered to replicate disease conditions influence senescence and fibrotic responses in primary lung fibroblasts.Frontiers in pharmacology · 2022Article
- Nobiletin promotes the pyroptosis of breast cancer via regulation of miR-200b/JAZF1 axis.The Kaohsiung journal of medical sciences · 2021Article
- Lysyl Oxidase-Like 4 Fosters an Immunosuppressive Microenvironment During Hepatocarcinogenesis.Hepatology (Baltimore, Md.) · 2021Article
- TGFβ-1 Induced Cross-Linking of the Extracellular Matrix of Primary Human Dermal Fibroblasts.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cutaneous fibrosis is a common complication seen in mixed connective tissue diseases. It often occurs as a result of TGF-β-induced deposition of excessive amounts of collagen in the skin. Lysyl oxidases (LOXs), a family of extracellular matrix (ECM)-modifying enzymes responsible for collagen cross-linking, are known to be increased in dermal fibroblasts from patients with fibrotic diseases, denoting a possible role of LOXs in fibrosis. To directly study this, we have developed two bioengineered, in vitro skin-like models: human skin equivalents (hSEs), and self-assembled stromal tissues (SASs) that contain either normal or systemic sclerosis (SSc; scleroderma) patient-derived fibroblasts. These tissues provide an organ-level structure that could be combined with non-invasive, label-free, multiphoton microscopy (SHG/TPEF) to reveal alterations in the organization and cross-linking levels of collagen fibers during the development of cutaneous fibrosis, which demonstrated increased stromal rigidity and activation of dermal fibroblasts in response to TGF-β1. Specifically, inhibition of specific LOXs isoforms, LOX and LOXL4, in foreskin fibroblasts (HFFs) resulted in antagonistic effects on TGF-β1-induced fibrogenic hallmarks in both hSEs and SASs. In addition, a translational relevance of these models was seen as similar antifibrogenic phenotypes were achieved upon knocking down LOXL4 in tissues containing SSc patient-derived-dermal fibroblasts (SScDFs). These findings point to a pivotal role of LOXs in TGF-β1-induced cutaneous fibrosis through impaired ECM homeostasis in skin-like tissues, and show the value of these tissue platforms in accelerating the discovery of antifibrosis therapeutics.
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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.