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Differential production of insulin-like growth factor-binding proteins in liver fibrosis progression

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Abstract

Noninvasive methods for liver disease diagnoses offer great advantages over biopsy, but they cannot be utilized in all cases. Therefore, specific indicators for chronic liver disease management are necessary. The aim was to assess the production of insulin-like growth factor-binding proteins (IGFBPs) 1–7 and their correlation with the different stages of fibrosis in chronic hepatitis C (CHC). A prospective, cross-sectional, multicenter study was conducted. CHC patients were categorized by FibroTest® and/or FibroScan®. Serum concentrations of IGFBPs 1–7 were determined through multiple suspension arrangement array technology. Significant differences were validated by the Kruskal–Wallis and Mann–Whitney U tests. Logistic regression models were performed to assess the association between the IGFBPs and fibrosis stages. The association was determined utilizing odds ratios (ORs), and receiver operating characteristic (ROC) curves were constructed to distinguish the IGFBPs in relation to the diagnosis of fibrosis. IGFBP-1 and IGFBP-7 concentrations were higher in CHC than in the healthy individuals, whereas IGFBP-3, IGFBP-5, and IGFBP-6 were downregulated in the patients. An apparent increase of all the IGFBPs was found at fibrosis stage F4, but with different regulations. IGFBP-2, -4, -6, and -7 had the best OR, showing the relation to fibrosis progression. The ROC curves showed that IGFBP-7 was the only protein that distinguished F1 from F3 and F2 from F3. IGFBPs participate in liver fibrosis progression and could be employed as circulating novel protein panels for diagnosis and as possible therapeutic targets in liver fibrosis progression.

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Acknowledgements

The present work is supported by the National Council for Science and Technology (CONACyT), Grant Number SALUD-2016-272579 and PAPIIT- UNAM TA200515 (to G-GR). The authors wish to thank the Postdoctoral Fellowship program at DGAPA-UNAM (to M-MC)

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Authors and Affiliations

  1. Liver, Pancreas and Motility Laboratory (HIPAM), Unit of Experimental Medicine, School of Medicine, National Autonomous University of Mexico (UNAM), General Hospital of Mexico, Mexico City, Mexico

    Moisés Martínez-Castillo, Dorothy Rosique-Oramas, Zaira Medina-Avila, David Kershenobich & Gabriela Gutierrez-Reyes

  2. General Hospital of Mexico “Dr. Eduardo Liceaga”, Mexico City, México

    José Luis Pérez-Hernández, Fatima Higuera-De la Tijera, Daniel Santana-Vargas & Eduardo Esteban Montalvo-Jave

  3. National Institute of Medical Sciences and Nutrition “Salvador Zubirán”, Mexico City, México

    Francico Sanchez-Avila, Aldo Torre & David Kershenobich

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  1. Moisés Martínez-Castillo
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Martínez-Castillo, M., Rosique-Oramas, D., Medina-Avila, Z. et al. Differential production of insulin-like growth factor-binding proteins in liver fibrosis progression. Mol Cell Biochem 469, 65–75 (2020). https://doi.org/10.1007/s11010-020-03728-4

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