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TWIST1 transcriptionally upregulates complement 3 in glomerular mesangial cells from spontaneously hypertensive rats

Hypertension Research volume 45, pages 66–74 (2022)Cite this article

Abstract

We have shown that complement 3 (C3) is upregulated in cardiovascular and renal organs, which induces the synthetic phenotype and exaggerates the growth of mesenchymal cells from spontaneously hypertensive rats (SHRs). However, the mechanisms of the upregulation of C3 have remained unclear. In the present study, we investigated the role of TWIST1, a transcription factor that regulates mesodermal embryogenesis, in the upregulation of C3 in glomerular mesangial cells (GMCs) from SHRs and Wistar–Kyoto (WKY) rats. Immunocytochemical staining and western blot analysis showed that the expression of TWIST1 in GMCs from SHRs was higher than that in GMCs from WKY rats in vivo and in vitro. Real-time PCR analysis showed increases in the expression of Twist1 mRNA with attenuated expression of miR-151-3p in GMCs from SHRs compared to that in cells from WKY rats. Chromatin immunoprecipitation assays showed increases in TWIST1 binding to the C3 promoter in GMCs from SHRs compared to that in cells from WKY rats. Transfection of Twist1 cDNA by a lentiviral vector increased the expression of C3 mRNA in GMCs from WKY rats. TWIST1 siRNA significantly decreased the mRNA expression of C3 and osteopontin in GMCs from SHRs. These results indicate that the increases in TWIST1 expression, attenuation of miR-151-3p, and strong binding of TWIST1 upregulate C3 gene expression in GMCs from SHRs. The enhanced TWIST1-C3 system induces the synthetic phenotype of mesenchymal tissue that may be associated with cardiovascular and renal remodeling in hypertension.

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Acknowledgements

The authors would like to thank Akiko Tsunemi and Mayumi Katakawa for their technical support.

Funding

This study was supported by a Grant-in-Aid for Scientific Research from MEXT 2015-2018 (15K09300).

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Authors and Affiliations

  1. Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, 173-8610, Japan

    Tomoyasu Otsuki, Noboru Fukuda, Takahiro Ueno, Masari Otsuki & Masanori Abe

  2. Division of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, Tokyo, 173-8610, Japan

    Noboru Fukuda & Lan Chen

Authors
  1. Tomoyasu Otsuki
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  2. Noboru Fukuda
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  3. Lan Chen
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  4. Takahiro Ueno
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  5. Masari Otsuki
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  6. Masanori Abe
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Contributions

Conceptualization, NF, MA; Methodology, NF; Validation, TO; Investigation, TO, LC; Data Curation, TU; Writing—Original Draft Preparation, TO; Writing—Review and Editing, NF, MA; Visualization, TO, NF; Supervision, NF, MA; Project Administration, NF, MA; Funding Acquisition, NF, MA. All authors approved the final version of the manuscript.

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Correspondence to Noboru Fukuda or Masanori Abe.

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Otsuki, T., Fukuda, N., Chen, L. et al. TWIST1 transcriptionally upregulates complement 3 in glomerular mesangial cells from spontaneously hypertensive rats. Hypertens Res 45, 66–74 (2022). https://doi.org/10.1038/s41440-021-00750-x

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