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Notch3 and its CADASIL mutants differentially regulate cellular phenotypes

  • Authors:
    • Chunjing Lin
    • Ziyang Huang
    • Riyong Zhou
    • Ying Zhou
    • Yangping Shentu
    • Kang Yu
    • Yu Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
    Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 117
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    Published online on: December 3, 2020
       https://doi.org/10.3892/etm.2020.9549
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Abstract

Notch3 is a member of the Notch family and its mutations are known to cause a hereditary human disorder called cerebral autosomal‑dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, the specific function and signaling cascade initiated by CADASIL mutants remain unknown. To gain further insight into mechanism of action of CADASIL mutants, the present study conducted several experiments on the effects of Notch3 mutants in multiple cell lines. The protein levels of Notch3, fibronectin, collagen, inducible nitric oxide synthase and DNA (cytosine‑5)‑methyltransferase 1 (DNMT1) were determined by western blotting. The mRNA levels of IL‑1β and TNF‑α were measured by reverse transcription semi‑quantitative PCR and DNMT1 mRNA levels were determined by quantitative PCR. Trypan blue staining was used for proliferation analysis and wound healing assays were performed to determine cell migration capability. The present study reported that R90C and R169C Notch3 mutants, and wild‑type Notch3 had different effects on several cell lines. In T/GHA‑VSMC cells, following the transfection of the two mutants, collagen and fibronectin expression increased, whereas expression decreased in IMR‑90 cells. In BV2 cells, the two mutants resulted in decreased nitric oxide and iNOS production. In HeLa cells, proliferation and migration increased significantly following the transfection of the two mutants, whereas in the MCF‑7 and HCC1937 cell lines, cell proliferation and migration decreased. In addition, the two mutants suppressed the expression of DNMT1 in HeLa and IMR‑90 cells. Overall, the present study provided novel insights that further explored the underlying mechanisms of CADASIL.
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Copy and paste a formatted citation
Spandidos Publications style
Lin C, Huang Z, Zhou R, Zhou Y, Shentu Y, Yu K and Zhang Y: Notch3 and its CADASIL mutants differentially regulate cellular phenotypes. Exp Ther Med 21: 117, 2021.
APA
Lin, C., Huang, Z., Zhou, R., Zhou, Y., Shentu, Y., Yu, K., & Zhang, Y. (2021). Notch3 and its CADASIL mutants differentially regulate cellular phenotypes. Experimental and Therapeutic Medicine, 21, 117. https://doi.org/10.3892/etm.2020.9549
MLA
Lin, C., Huang, Z., Zhou, R., Zhou, Y., Shentu, Y., Yu, K., Zhang, Y."Notch3 and its CADASIL mutants differentially regulate cellular phenotypes". Experimental and Therapeutic Medicine 21.2 (2021): 117.
Chicago
Lin, C., Huang, Z., Zhou, R., Zhou, Y., Shentu, Y., Yu, K., Zhang, Y."Notch3 and its CADASIL mutants differentially regulate cellular phenotypes". Experimental and Therapeutic Medicine 21, no. 2 (2021): 117. https://doi.org/10.3892/etm.2020.9549
Copy and paste a formatted citation
x
Spandidos Publications style
Lin C, Huang Z, Zhou R, Zhou Y, Shentu Y, Yu K and Zhang Y: Notch3 and its CADASIL mutants differentially regulate cellular phenotypes. Exp Ther Med 21: 117, 2021.
APA
Lin, C., Huang, Z., Zhou, R., Zhou, Y., Shentu, Y., Yu, K., & Zhang, Y. (2021). Notch3 and its CADASIL mutants differentially regulate cellular phenotypes. Experimental and Therapeutic Medicine, 21, 117. https://doi.org/10.3892/etm.2020.9549
MLA
Lin, C., Huang, Z., Zhou, R., Zhou, Y., Shentu, Y., Yu, K., Zhang, Y."Notch3 and its CADASIL mutants differentially regulate cellular phenotypes". Experimental and Therapeutic Medicine 21.2 (2021): 117.
Chicago
Lin, C., Huang, Z., Zhou, R., Zhou, Y., Shentu, Y., Yu, K., Zhang, Y."Notch3 and its CADASIL mutants differentially regulate cellular phenotypes". Experimental and Therapeutic Medicine 21, no. 2 (2021): 117. https://doi.org/10.3892/etm.2020.9549
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