ArticleThe American journal of pathology2008
Insulin-like growth factor-II is increased in systemic sclerosis-associated pulmonary fibrosis and contributes to the fibrotic process via Jun N-terminal kinase- and phosphatidylinositol-3 kinase-dependent pathways.
Article in The American journal of pathology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- MRI Assessment of Treatment Response in HIV-associated NAFLD: A Randomized Trial of a Stearoyl-Coenzyme-A-Desaturase-1 Inhibitor (ARRIVE Trial).Hepatology (Baltimore, Md.) · 2019Trial
- Comparison of the Transcriptomic Signatures of Skin and Lung Fibroblasts from Patients with Systemic Sclerosis.Fibrosis (Hong Kong, China) · 2026Article
- Role of Growth Factors in the Pathogenesis of Systemic-Sclerosis-Associated Fibrosis.International journal of molecular sciences · 2025Review
- Mechanical stretch-induced IGF2 overexpression in epidermal keratinocytes promotes hypertrophic scar formation through the IGF1R/p-c-Jun axis.International journal of biological sciences · 2025Article
- A review of recent studies on the pathogenesis of Systemic Sclerosis: focus on fibrosis pathways.Frontiers in immunology · 2025Review
- Decoding the enigmatic estrogen paradox in pulmonary hypertension: delving into estrogen metabolites and metabolic enzymes.Cellular & molecular biology letters · 2024Review
- IGF-II regulates lysyl oxidase propeptide and mediates its effects in part via basic helix-loop-helix E40.Matrix biology : journal of the International Society for Matrix Biology · 2024Article
- Single-Cell RNA-Sequencing Analyses Identify APLNR, INS-IGF2, RGCC Genes May Be Involved in the Pathogenesis of Systemic Sclerosis Skin.Clinical, cosmetic and investigational dermatology · 2024Article
- Glycolysis and beyond in glucose metabolism: exploring pulmonary fibrosis at the metabolic crossroads.Frontiers in endocrinology · 2024Review
- Cellular Transdifferentiation: A Crucial Mechanism of Fibrosis in Systemic Sclerosis.Current rheumatology reviews · 2024Review
- The Role of SOX9 in IGF-II-Mediated Pulmonary Fibrosis.International journal of molecular sciences · 2023Article
- First Characterization of the Transcriptome of Lung Fibroblasts of SSc Patients and Healthy Donors of African Ancestry.International journal of molecular sciences · 2023Article
- The Molecular Mechanisms of Systemic Sclerosis-Associated Lung Fibrosis.International journal of molecular sciences · 2023Review
- Pulmonary Fibrosis as a Result of Acute Lung Inflammation: Molecular Mechanisms, Relevant In Vivo Models, Prognostic and Therapeutic Approaches.International journal of molecular sciences · 2022Review
- Insulin-like Growth Factor-2 (IGF-2) in Fibrosis.Biomolecules · 2022Review
- Pregnancy-associated plasma protein-A (PAPP-A) is a key component of an interactive cellular mechanism promoting pulmonary fibrosis.Journal of cellular physiology · 2022Article
- Prognostic utility of magnetic resonance elastography and MEFIB index in predicting liver-related outcomes and mortality in individuals at risk of and with nonalcoholic fatty liver disease.Therapeutic advances in gastroenterology · 2022Article
- The impact of genetic risk on liver fibrosis in non-alcoholic fatty liver disease as assessed by magnetic resonance elastography.Alimentary pharmacology & therapeutics · 2021Article
- Engineering Advanced In Vitro Models of Systemic Sclerosis for Drug Discovery and Development.Advanced biology · 2021Review
- Pulmonary involvement in systemic sclerosis: exploring cellular, genetic and epigenetic mechanisms.Rheumatology international · 2020Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Systemic sclerosis (SSc)-related pulmonary fibrosis, for which there are few effective therapies, is the most common cause of SSc-related mortality. We examined insulin-like growth factor (IGF)-II expression in explanted lung tissues from control and SSc patients to determine its role in the pathogenesis of fibrosis. IGF-II levels in vivo were detected using immunohistochemistry. Primary lung fibroblasts were cultured from lung tissues, and IGF-II mRNA was measured using reverse transcriptase-polymerase chain reaction. Western blot analysis measured extracellular matrix (ECM) production and phosphorylated signaling molecules. Immunostaining revealed increased IGF-II expression in fibroblastic foci of SSc lungs. Furthermore, primary SSc lung fibroblasts had a fourfold increase in IGF-II mRNA and a twofold increase in IGF-II protein compared with normal lung fibroblasts. IGF-II mRNA in SSc lung fibroblasts was expressed primarily from the P3 promoter of the IGF-II gene, and IGF-II induced both a dose- and time-dependent increase in collagen type I and fibronectin production. IGF-II triggered the activation of both phosphatidylinositol-3 kinase and Jun N-terminal kinase signaling cascades, the inhibition of which diminished IGF-II-induced ECM production. Our study demonstrates increased local IGF-II expression in SSc-associated pulmonary fibrosis both in vitro and in vivo as well as IGF-II-induced ECM production through both phosphatidylinositol-3 kinase- and Jun N-terminal kinase-dependent pathways. Our results provide novel insights into the role of IGF-II in the pathogenesis of SSc-associated pulmonary fibrosis.
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