IL-17 induces myocardial fibrosis and enhances RANKL/OPG and MMP/TIMP signaling in isoproterenol-induced heart failure
Abstract
Objective This study was designed to investigate whether IL-17 can regulate the expression of the MMP/TIMP system, the OPG/RANK/RANKL system, or type-I and type-III collagen fibers in a rat model of isoproterenol-induced heart failure (HF). We also investigated the effect of IL-17 on myocardial fibrosis in this model.Methods HF was induced in Wistar-Kyoto rats by hypodermic injection of isoproterenol (ISO) twice every 24 h. After 2 months, the surviving rats were divided into three groups: monoclonal Anti-IL-17 Ab (100 microg/day), IgG (100 microg/day) or PBS were injected five times every 48 h (i.p.). One day after the last injection, all of the rats were sacrificed. H&E and Masson staining were used to evaluate myocardial fibrosis, and immunohistochemistry was used to measure the levels of MMP-1, TIMP-1, TIMP-4, OPG, RANKL, type-I and type-III collagen fibers. We also treated adult rat cardiac fibroblasts with IL-17 (10 ng/ml), IL-17 (10 ng/ml)+OPG (10 ng/ml), IL-17 (10 ng/ml)+anti-RANKL Ab (100 ng/ml), or PBS for 24 h, realtime RT-PCR was used to measure the expressions of MMP-1.Results The expressions of MMP-1, RANKL, and type-I and -III collagen fibers decreased, and the expressions of TIMP-1, TIMP-4, and OPG increased in the Anti-IL-17 group compared to controls. H&E and Masson staining revealed that blockade of IL-17 can improve myocardial fibrosis in HF. IL-17 increased the expression of MMP-1 in cardiac fibroblasts, and OPG and anti-IL-17 Ab could inhibit this function partly. Thus, IL-17 was dependent on the RANKL/OPG system to induce MMP-1 partly.Conclusion Our study demonstrates the contribution of IL-17 to myocardial fibrosis in isoproterenol-induced HF. IL-17 can regulate the RANKL/OPG and MMP/TIMP systems in this model. The RANKL/OPG system is one of intermediaries between IL-17 and MMP-1 in cardiac fibroblasts. As a harmful cytokine, anti-IL-17 treatment is a potential therapeutic strategy in HF.
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IL-17A exhibits similar pro-fibrotic activity in animal studies and in human cells.
“IL-17A exhibited similar pro-fibrotic activity in both animal studies and in human cells124,125”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [124]
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- Authors
- Feng, W., Li, W., Liu, W., Wang, F., Li, Y., & Yan, W.
- Affiliations
- Harbin Medical University (CN)
- Corresponding author
- Li, Weimin
- Venue
- Experimental and Molecular Pathology
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 87
- Issue
- 3
- Pages
- 212-218
- ISSN
- 0014-4800 (ISSN-L)
- OpenAlex
- W2089365645
- Cited by
- 139
- References
- 31
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 6 · 2023: 4 · 2022: 6 · 2021: 7 · 2020: 9 · 2019: 12 · 2018: 5 · 2017: 11 · 2016: 8 · 2015: 9 · 2014: 10 · 2013: 12 · 2012: 15
- FWCI
- 5.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental and Molecular Pathology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Harbin Medical University (2007033)
- National Natural Science Foundation of China (30800481)
- Ministry of Education (20070226005)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Keywords
- IL-17, myocardial fibrosis, heart failure, isoproterenol-induced heart failure, RANKL/OPG signaling, MMP-1, TIMP-1, TIMP-4, type I collagen, type III collagen, cardiac fibroblasts, anti-IL-17 antibody, inflammation in heart failure, matrix metalloproteinases, osteoprotegerin
- MeSH terms
- Animals, Disease Models, Animal, Fibrosis, Heart Failure, Isoproterenol, Male, Myocardium, Signal Transduction, Rats, Wistar, Tissue Inhibitor of Metalloproteinases, Interleukin-17, Matrix Metalloproteinases, Rats, Osteoprotegerin, RANK Ligand
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