ArticleThe Journal of biological chemistry2011
Fibromodulin suppresses nuclear factor-kappaB activity by inducing the delayed degradation of IKBA via a JNK-dependent pathway coupled to fibroblast apoptosis.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- From Proteome to miRNome: A Review of Multi-Omics Ocular Allergy Research Using Human Tears.International journal of molecular sciences · 2026Review
- Mmp14-dependent remodeling of the pericellular-dermal collagen interface governs fibroblast survival.The Journal of cell biology · 2024Article
- Biomimetic strategies for the deputization of proteoglycan functions.Frontiers in cell and developmental biology · 2024Review
- Fibromodulin overexpression drives oral squamous cell carcinoma via activating downstream EGFR signaling.iScience · 2023Article
- Corilagin ameliorates macrophages inflammation in atherosclerosis through TLR4-NFκB/MAPK pathway.Heliyon · 2023Article
- Uncovering the immune microenvironment and molecular subtypes of hepatitis B-related liver cirrhosis and developing stable a diagnostic differential model by machine learning and artificial neural networks.Frontiers in molecular biosciences · 2023Article
- Fibromodulin Ablation Exacerbates the Severity of Acute Colitis.Journal of inflammation research · 2022Article
- miR-370-3p as a Novel Biomarker Promotes Breast Cancer Progression by Targeting FBLN5.Stem cells international · 2021Article
- Communications via the Small Leucine-rich Proteoglycans: Molecular Specificity in Inflammation and Autoimmune Diseases.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020Review
- Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways.BMC immunology · 2020Article
- Proteoglycans in Biomedicine: Resurgence of an Underexploited Class of ECM Molecules.Frontiers in pharmacology · 2019Review
- The role of fibromodulin in cancer pathogenesis: implications for diagnosis and therapy.Cancer cell international · 2019Review
- Extracellular Interactions between Fibulins and Transforming Growth Factor (TGF)-β in Physiological and Pathological Conditions.International journal of molecular sciences · 2018Review
- Recombinant fibromodulin and decorin effects on NF-κB and TGFβ1 in the 4T1 breast cancer cell line.Oncology letters · 2017Article
- Stromal Modulators of TGF-β in Cancer.Journal of clinical medicine · 2017Review
- Novel insights into the function and dynamics of extracellular matrix in liver fibrosis.American journal of physiology. Gastrointestinal and liver physiology · 2015Review
- Differential network analysis reveals dysfunctional regulatory networks in gastric carcinogenesis.American journal of cancer research · 2015Article
- Quantitative Proteomic Profiling of Low-Dose Ionizing Radiation Effects in a Human Skin Model.Proteomes · 2014Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Fibulin-5 (FBLN5) belongs to the Fibulin family of secreted extracellular matrix proteins, and our laboratory first established FBLN5 as a novel target for TGF-β in fibroblasts and endothelial cells. To better understand the pathophysiology of FBLN5, we carried out microarray analysis to identify fibroblast genes whose expressions were regulated by FBLN5 and TGF-β. In doing so, we identified fibromodulin (Fmod) as a novel target gene of FBLN5, and we validated the differential expression of Fmod and 12 other FBLN5-regulated genes by semi-quantitative real time PCR. Fmod belongs to the small leucine-rich family of proteoglycans, which are important constituents of mammalian extracellular matrices. Interestingly, parental 3T3-L1 fibroblasts displayed high levels of nuclear factor-κB (NF-κB) activity, although those engineered to express Fmod constitutively exhibited significantly reduced NF-κB activity, suggesting that Fmod functions to inhibit NF-κB signaling. By monitoring alterations in the activation of NF-κB and the degradation of its inhibitor, IκBα, we demonstrate for the first time that Fmod contributes to the constitutive degradation of IκBα protein in 3T3-L1 fibroblasts. Mechanistically, we observed Fmod to delay the degradation of IκBα by promoting the following: (i) activation of c-Jun N-terminal kinase; (ii) inhibition of calpain and casein kinase 2 activity; and (iii) induction of fibroblast apoptosis. Taken together, our study identified a novel function for Fmod in directing extracellular signaling, particularly the regulation of NF-κB activity and cell survival.
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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.