Abstract
Cardiac fibrosis is a remodeling process of the cardiac interstitium, characterized by abnormal metabolism of the extracellular matrix, excessive accumulation of collagen fibers, and scar tissue hyperplasia. Persistent activation and transdifferentiation into myofibroblasts of cardiac fibroblasts promote the progression of fibrosis. Transforming growth factor-β1 (TGF-β1) is a pivotal factor in cardiac fibrosis. Latency-associated peptide (LAP) is essential for activating TGF-β1 and its binding to the receptor. Thus, interference with TGF-β1 and the signaling pathways using LAP may attenuate cardiac fibrosis. Recombinant full-length and truncated LAP were previously constructed, expressed, and purified. Their effects on cardiac fibrosis were investigated in isoproterenol (ISO)-induced cardiac fibroblasts (CFs) and C57BL/6 mice. The study showed that LAP and tLAP inhibited ISO-induced CF activation, inflammation, and fibrosis, improved cardiac function, and alleviated myocardial injury in ISO-induced mice. LAP and tLAP alleviated the histopathological alterations and inhibited the elevated expression of inflammatory and fibrosis-related markers in cardiac tissue. In addition, LAP and tLAP decreased the ISO-induced elevated expression of TGF-β, αvβ3, αvβ5, p-Smad2, and p-Smad3. The study indicated that LAP and tLAP attenuated ISO-induced cardiac fibrosis via suppressing TGF-β/Smad pathway. This study may provide a potential approach to alleviate cardiac fibrosis.
Key points
• LAP and tLAP inhibited ISO-induced CF activation, inflammation, and fibrosis.
• LAP and tLAP improved cardiac function and alleviated myocardial injury, inflammation, and fibrosis in ISO-induced mice.
• LAP and tLAP attenuated cardiac fibrosis via suppressing TGF-β/Smad pathway.
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Data availability
The datasets generated during the study are available from the corresponding author on reasonable request.
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Funding
This study was supported by the Natural Science Foundation of Heilongjiang Province (Outstanding Youth Project, Grant No. YQ2020H026), Central Finance supports Local Colleges, and Universities Talent Development Funding from Heilongjiang Provincial Department of Finance (High Level Talent Support Project, Grant No. 2020GSP09), Torch Program Youth Top Talent Project of Mudanjiang Medical University (Grant No. 2022-MYHJ-015), Doctoral Research Foundation of Mudanjiang Medical University (Grant No. 2021-MYBSKY-066), and Scientific research project of Health Commission of Heilongjiang Province (Grant No. 20220101040974).
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DW and XHY conceived and designed research. YFQ, XDS, ZQC, KKZ, and JRL conducted experiments. YW, YL, and YHC contributed new reagents or analytical tools. JYS, FZ, and YP analyzed data. YFQ and XDS wrote the manuscript. DW revised the manuscript. All authors read and approved the manuscript.
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The study was approved by the Institutional Animal Care and Use Committee of Mudanjiang Medical University (IACUC-20210702–9).
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Qiu, Y., Song, X., Liu, Y. et al. Application of recombinant TGF-β1 inhibitory peptide to alleviate isoproterenol-induced cardiac fibrosis. Appl Microbiol Biotechnol 107, 6251–6262 (2023). https://doi.org/10.1007/s00253-023-12722-x
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DOI: https://doi.org/10.1007/s00253-023-12722-x