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Analysis of gene expression profiling of amyloidogenic immunoglobulin light‑chains on cultured rat cardiomyocytes

  • Authors:
    • Fei Xu
    • Yue Yu
    • Fang Wang
    • Wei Sun
    • Peng Li
    • Heng‑Fang Wu
    • Zhi‑Ping Bian
    • Xiang‑Jian Chen
    • Dong‑Jie Xu
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
    Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3767-3777
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    Published online on: March 19, 2020
       https://doi.org/10.3892/etm.2020.8610
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Abstract

The present study aimed to investigate the toxic effects of different amyloidogenic light‑chains (LCs) on cardiomyocytes, and demonstrate the differentially expressed genes (DEGs) and signaling pathways that participate in this process. Cultured cardiomyocytes were treated with recombinant κ LC peptide (AL‑09) or with serum from a patient diagnosed with multiple myeloma (λ LC) with cardiac involvement. The 6xHis peptide or serum from healthy patients was used as peptide control or serum control, respectively. Cell viability was determined using CCK‑8 assay and apoptosis was analyzed by flow cytometry. The DEGs were detected by RNA sequencing (RNA‑Seq), followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Changes in gene expression levels were confirmed by reverse transcription‑quantitative PCR. The cell viability in the AL‑09 peptide‑treated (0.2 mg/ml) and patient serum‑treated (1:10 dilution) cardiomyocytes decreased to 42 and ‑72% of the corresponding control groups. The extent of cell apoptosis increased in AL‑09‑treated cardiomyocytes compared with the control group. RNA‑Seq showed 256 DEGs co‑existed in the two paired groups, including 127 upregulated and 88 downregulated genes. The KEGG pathways for upregulated expressed genes included the ‘TGF‑β signaling pathway’, the ‘Hedgehog signaling pathway’, the ‘ErbB signaling pathway’ and ‘lysine degradation’. The higher mRNA expression of bone morphogenetic protein (Bmp) 4, Bmp6, prostaglandin G/H synthase (Ptgs)1, Ptgs2, epiregulin, Tgfa and procollagen‑lysine,2‑oxoglutarate 5‑dioxygenase 2 were confirmed. The KEGG pathways of downregulated expressed genes included genes involved with the ‘p53 signaling pathway’ and the ‘cell cycle’. The mRNA expression levels of E3 ubiquitin‑protein ligase CCNB1IP1 showed significant downregulation in the AL‑09 peptide group compared with those in the 6xHis peptide group. In conclusion, cardiomyocytes treated with amyloidogenic λ and κ LCs presented with decreased cell viability compared with controls. Cell apoptosis increased in κ LC‑treated cells compared with controls. The gene expression profiles associated with transforming growth factor‑β‑bone morphogenetic protein, the receptor tyrosine‑protein kinase erbB‑2 signaling pathways, prostaglandins, collagen production, the p53 signaling pathway and the cell cycle were altered in light‑chain‑treated cardiomyocytes.
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Copy and paste a formatted citation
Spandidos Publications style
Xu F, Yu Y, Wang F, Sun W, Li P, Wu HF, Bian ZP, Chen XJ and Xu DJ: Analysis of gene expression profiling of amyloidogenic immunoglobulin light‑chains on cultured rat cardiomyocytes. Exp Ther Med 19: 3767-3777, 2020.
APA
Xu, F., Yu, Y., Wang, F., Sun, W., Li, P., Wu, H. ... Xu, D. (2020). Analysis of gene expression profiling of amyloidogenic immunoglobulin light‑chains on cultured rat cardiomyocytes. Experimental and Therapeutic Medicine, 19, 3767-3777. https://doi.org/10.3892/etm.2020.8610
MLA
Xu, F., Yu, Y., Wang, F., Sun, W., Li, P., Wu, H., Bian, Z., Chen, X., Xu, D."Analysis of gene expression profiling of amyloidogenic immunoglobulin light‑chains on cultured rat cardiomyocytes". Experimental and Therapeutic Medicine 19.6 (2020): 3767-3777.
Chicago
Xu, F., Yu, Y., Wang, F., Sun, W., Li, P., Wu, H., Bian, Z., Chen, X., Xu, D."Analysis of gene expression profiling of amyloidogenic immunoglobulin light‑chains on cultured rat cardiomyocytes". Experimental and Therapeutic Medicine 19, no. 6 (2020): 3767-3777. https://doi.org/10.3892/etm.2020.8610
Copy and paste a formatted citation
x
Spandidos Publications style
Xu F, Yu Y, Wang F, Sun W, Li P, Wu HF, Bian ZP, Chen XJ and Xu DJ: Analysis of gene expression profiling of amyloidogenic immunoglobulin light‑chains on cultured rat cardiomyocytes. Exp Ther Med 19: 3767-3777, 2020.
APA
Xu, F., Yu, Y., Wang, F., Sun, W., Li, P., Wu, H. ... Xu, D. (2020). Analysis of gene expression profiling of amyloidogenic immunoglobulin light‑chains on cultured rat cardiomyocytes. Experimental and Therapeutic Medicine, 19, 3767-3777. https://doi.org/10.3892/etm.2020.8610
MLA
Xu, F., Yu, Y., Wang, F., Sun, W., Li, P., Wu, H., Bian, Z., Chen, X., Xu, D."Analysis of gene expression profiling of amyloidogenic immunoglobulin light‑chains on cultured rat cardiomyocytes". Experimental and Therapeutic Medicine 19.6 (2020): 3767-3777.
Chicago
Xu, F., Yu, Y., Wang, F., Sun, W., Li, P., Wu, H., Bian, Z., Chen, X., Xu, D."Analysis of gene expression profiling of amyloidogenic immunoglobulin light‑chains on cultured rat cardiomyocytes". Experimental and Therapeutic Medicine 19, no. 6 (2020): 3767-3777. https://doi.org/10.3892/etm.2020.8610
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