General Physiology and Biophysics Vol.39, No.2, 187–194, 2020
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Title: CXCR4 antagonist alleviates proliferation and collagen synthesis
of cardiac fibroblasts induced by TGF-β1 |
Author: Wei Wang, Chuntao Wu, Rong Luo, Zheng Zhang |
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Abstract: We aimed to investigate the effects of CX-C chemokine receptor type 4 (CXCR4) on transforming growth factor (TGF)-β1-induced cardiac fibrosis in Human cardiac fibroblasts (HCFs). HCFs were stimulated with TGF-β1, and the level of α-smooth muscle actin (α-SMA) was assessed by immunofluorescence assay. The expression of CXCR4 was detected by Western blotting. Then the cells were incubated with CXCR4 antagonist AMD 3465. Cell viability was measured by CCK-8 assay. The expression of α-SMA, proliferating cell nuclear antigen (PCNA) and Ki67 were examined. Collagen synthesis was detected by sirius red staining. Moreover, the expression of phpspho-Smad2 (p-Smad2) and p-Smad3 were determined. We found that the level of α-SMA was increased after induction with TGF-β1. The expression of CXCR4 was upregulated in TGF-β1-treated HCFs. Following treatment with AMD 3465, cell proliferation was inhibited coupled with a decrease in PCNA and Ki67 expression. Additionally, the expression of α-SMA was decreased after being intervened with AMD 3465. Concurrently, the levels of collagen were reduced accompanied by downregulation of Collagen I and III. Furthermore, AMD 3465 treatment decreased the expression of p-Smad2 and p-Smad3. Our findings suggested that CXCR4 antagonist AMD 3465 could alleviate cardiac fibrosis via blocking TGF-β1-induced activation of Smad2/3 in HCFs.
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Keywords: CX-C chemokine receptor type 4 — AMD 3465 — TGF-β1 — Cardiac fibrosis — Collagen |
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Published online: 26-Mar-2020
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Year: 2020, Volume: 67, Issue: 2 |
Page From: 187, Page To: 194 |
doi:10.4149/gpb_2019051
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