Open Access

Human umbilical cord mesenchymal stem cells alleviate interstitial fibrosis and cardiac dysfunction in a dilated cardiomyopathy rat model by inhibiting TNF‑α and TGF‑β1/ERK1/2 signaling pathways

  • Authors:
    • Changyi Zhang
    • Guichi Zhou
    • Yezeng Chen
    • Sizheng Liu
    • Fen Chen
    • Lichun Xie
    • Wei Wang
    • Yonggang Zhang
    • Tianyou Wang
    • Xiulan Lai
    • Lian Ma
  • View Affiliations

  • Published online on: October 26, 2017     https://doi.org/10.3892/mmr.2017.7882
  • Pages:71-78
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dilated cardiomyopathy (DCM) is a disease of the heart characterized by pathological remodeling, including patchy interstitial fibrosis and degeneration of cardiomyocytes. In the present study, the beneficial role of human umbilical cord‑derived mesenchymal stem cells (HuMSCs) derived from Wharton's jelly was evaluated in the myosin‑induced rat model of DCM. Male Lewis rats (aged 8‑weeks) were injected with porcine myosin to induce DCM. Cultured HuMSCs (1x106 cells/rat) were intravenously injected 28 days after myosin injection and the effects on myocardial fibrosis and the underlying signaling pathways were investigated and compared with vehicle‑injected and negative control rats. Myosin injections in rats (vehicle group and experimental group) for 28 days led to severe fibrosis and significant deterioration of cardiac function indicative of DCM. HuMSC treatment reduced fibrosis as determined by Masson's staining of collagen deposits, as well as quantification of molecular markers of myocardial fibrosis such as collagen I/III, profibrotic factors transforming growth factor‑β1 (TGF‑β1), tumor necrosis factor‑α (TNF‑α), and connective tissue growth factor (CTGF). HuMSC treatment restored cardiac function as observed using echocardiography. In addition, western blot analysis indicated that HuMSC injections in DCM rats inhibited the expression of TNF‑α, extracellular‑signal regulated kinase 1/2 (ERK1/2) and TGF‑β1, which is a master switch for inducing myocardial fibrosis. These findings suggested that HuMSC injections attenuated myocardial fibrosis and dysfunction in a rat model of DCM, likely by inhibiting TNF‑α and the TGF‑β1/ERK1/2 fibrosis pathways. Therefore, HuMSC treatment may represent a potential therapeutic method for treatment of DCM.

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January 2018
Volume 17 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

2016 Impact Factor: 1.692
Ranked #19/128 Medicine Research and Experimental
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APA
Zhang, C., Zhou, G., Chen, Y., Liu, S., Chen, F., Xie, L. ... Ma, L. (2018). Human umbilical cord mesenchymal stem cells alleviate interstitial fibrosis and cardiac dysfunction in a dilated cardiomyopathy rat model by inhibiting TNF‑α and TGF‑β1/ERK1/2 signaling pathways. Molecular Medicine Reports, 17, 71-78. https://doi.org/10.3892/mmr.2017.7882
MLA
Zhang, C., Zhou, G., Chen, Y., Liu, S., Chen, F., Xie, L., Wang, W., Zhang, Y., Wang, T., Lai, X., Ma, L."Human umbilical cord mesenchymal stem cells alleviate interstitial fibrosis and cardiac dysfunction in a dilated cardiomyopathy rat model by inhibiting TNF‑α and TGF‑β1/ERK1/2 signaling pathways". Molecular Medicine Reports 17.1 (2018): 71-78.
Chicago
Zhang, C., Zhou, G., Chen, Y., Liu, S., Chen, F., Xie, L., Wang, W., Zhang, Y., Wang, T., Lai, X., Ma, L."Human umbilical cord mesenchymal stem cells alleviate interstitial fibrosis and cardiac dysfunction in a dilated cardiomyopathy rat model by inhibiting TNF‑α and TGF‑β1/ERK1/2 signaling pathways". Molecular Medicine Reports 17, no. 1 (2018): 71-78. https://doi.org/10.3892/mmr.2017.7882