ArticleThe American journal of pathology2009
The fibrotic phenotype induced by IGFBP-5 is regulated by MAPK activation and egr-1-dependent and -independent mechanisms.
Article in The American journal of pathology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 68 citations in OpenAlex.
- Low-dose nicotine enhances arecoline-induced human oral mucosa fibroblast proliferation by stabilizing Egr-1 protein.Odontology · 2026Article
- Multi-omics analysis identifies fibroblast IGFBP5 as a key target of anti-TNFα therapy in ulcerative colitis.Frontiers in immunology · 2026Article
- Mechanisms of endothelial senescence and vascular aging.Biogerontology · 2025Review
- The Role of SOX9 in IGF-II-Mediated Pulmonary Fibrosis.International journal of molecular sciences · 2023Article
- Insulin-like growth factor binding protein 5b ofFrontiers in immunology · 2023Article
- Defining the spatial-molecular map of fibrotic tendon healing and the drivers of Scleraxis-lineage cell fate and function.Cell reports · 2022Article
- Insulin-like growth factor binding protein 5: Diverse roles in cancer.Frontiers in oncology · 2022Review
- Colon stroma mediates an inflammation-driven fibroblastic response controlling matrix remodeling and healing.PLoS biology · 2022Article
- Identification of Impacted Pathways and Transcriptomic Markers as Potential Mediators of Pulmonary Fibrosis in Transgenic Mice Expressing Human IGFBP5.International journal of molecular sciences · 2021Article
- Elucidating the cellular mechanism for E2-induced dermal fibrosis.Arthritis research & therapy · 2021Article
- Induced organoids derived from patients with ulcerative colitis recapitulate colitic reactivity.Nature communications · 2021Article
- The Potential Use of Cannabis in Tissue Fibrosis.Frontiers in cell and developmental biology · 2021Review
- Gene expression profiling of fibroblasts in a family with LMNA-related cardiomyopathy reveals molecular pathways implicated in disease pathogenesis.BMC medical genetics · 2020Article
- EGR1 Transcription Factor is a Multifaceted Regulator of Matrix Production in Tendons and Other Connective Tissues.International journal of molecular sciences · 2020Review
- Prominence of IL6, IGF, TLR, and Bioenergetics Pathway Perturbation in Lung Tissues of Scleroderma Patients With Pulmonary Fibrosis.Frontiers in immunology · 2020Article
- PAPP-A and the IGF system in atherosclerosis: what's up, what's down?American journal of physiology. Heart and circulatory physiology · 2019Review
- Adult and iPS-derived non-parenchymal cells regulate liver organoid development through differential modulation of Wnt and TGF-β.Stem cell research & therapy · 2019Article
- NADPH oxidase-mediated induction of reactive oxygen species and extracellular matrix deposition by insulin-like growth factor binding protein-5.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Insulin-like growth factor binding protein-4 exerts antifibrotic activity by reducing levels of connective tissue growth factor and the C-X-C chemokine receptor 4.FASEB bioAdvances · 2019Article
- IGFBP-5 Promotes Fibrosis via Increasing Its Own Expression and That of Other Pro-fibrotic Mediators.Frontiers in endocrinology · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
We have previously shown that insulin-like growth factor (IGF) binding protein- 5 (IGFBP-5) is overexpressed in lung fibrosis and induces the production of extracellular matrix components, such as collagen and fibronectin, both in vitro and in vivo. The exact mechanism by which IGFBP-5 exerts these novel fibrotic effects is unknown. We thus examined the signaling cascades that mediate IGFBP-5-induced fibrosis. We demonstrate for the first time that IGFBP-5 induction of extracellular matrix occurs independently of IGF-I, and results from IGFBP-5 activation of MAPK signaling, which facilitates the translocation of IGFBP-5 to the nucleus. We examined the effects of IGFBP-5 on early growth response (Egr)-1, a transcription factor that is central to growth factor-mediated fibrosis. Egr-1 was up-regulated by IGFBP-5 in a MAPK-dependent manner and bound to nuclear IGFBP-5. In fibroblasts from Egr-1 knockout mice, induction of fibronectin by IGFBP-5 was abolished. Expression of Egr-1 in these cells rescued the extracellular matrix-promoting effects of IGFBP-5. Moreover, IGFBP-5 induced cell migration in an Egr-1-dependent manner. Notably, Egr-1 levels, similar to IGFBP-5, were increased in vivo in lung tissues and in vitro in primary fibroblasts of patients with pulmonary idiopathic fibrosis. Taken together, our findings suggest that IGFBP-5 induces a fibrotic phenotype via the activation of MAPK signaling and the induction of nuclear Egr-1 that interacts with IGFBP-5 and promotes fibrotic gene transcription.
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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.