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Cited by 3Mesenchymal stem cell researchConnective Tissue Growth Factor ResearchAngiogenesis and VEGF in Cancer

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Knockdown SENP1 Suppressed the Angiogenic Potential of Mesenchymal Stem Cells by Impacting CXCR4-Regulated MRTF-A SUMOylation and CCN1 Expression

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Zhang, Rui, Liu, Qingxi, Lyu, Cuicui, Gao, Xing, Ma, Wenjian·2023·Biomedicines
DOI 10.3390/biomedicines11030914PMC PMC10046070
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Abstract

The angiogenic potential of mesenchymal stem cells (MSCs) is critical for adult vascular regeneration and repair, which is regulated by various growth factors and cytokines. In the current study, we report that knockdown SUMO-specific peptidase 1 (SENP1) stimulated the SUMOylation of MRTF-A and prevented its translocation into the nucleus, leading to downregulation of the cytokine and angiogenic factor CCN1, which significantly impacted MSC-mediated angiogenesis and cell migration. Further studies showed that SENP1 knockdown also suppressed the expression of a chemokine receptor CXCR4, and overexpression of CXCR4 could partially abrogate MRTF-A SUMOylation and reestablish the CCN1 level. Mutation analysis confirmed that SUMOylation occurred on three lysine residues (Lys-499, Lys-576, and Lys-624) of MRTF-A. In addition, SENP1 knockdown abolished the synergistic co-activation of CCN1 between MRTF-A and histone acetyltransferase p300 by suppressing acetylation on histone3K9, histone3K14, and histone4. These results revealed an important signaling pathway to regulate MSC differentiation and angiogenesis by MRTF-A SUMOylation involving cytokine/chemokine activities mediated by CCN1 and CXCR4, which may potentially impact a variety of cellular processes such as revascularization, wound healing, and progression of cancer.

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Metadata

Authors
Zhang, R., Liu, Q., Lyu, C., Gao, X., & Ma, W.
Affiliations
  • Nankai University (CN)
  • Qilu University of Technology (CN)
  • Tianjin University of Science and Technology (CN)
Corresponding author
  • Liu, Qingxi
  • Ma, Wenjian
ORCID
Venue
Biomedicines
Publisher
MDPI AG
Published
2023-03-15
Volume
11
Issue
3
Pages
914
ISSN
2227-9059 (ISSN-L)
DOI
10.3390/biomedicines11030914
PMC
PMC10046070
OpenAlex
W4327595726
Cited by
3
References
2
Citations by year
2025: 1 · 2024: 2
FWCI
0.52
Type
journal article
Language
en
Open access
Licence
Locations
  • Biomedicines (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Key R&D Program of China (2018YFA0901702, TJYXZDXK-056B, 2019GSF107088, ZR2020MC077, ZR202111220001)
  • Tianjin Key Medical Discipline (Specialty) Construction Project (2018YFA0901702, TJYXZDXK-056B, 2019GSF107088, ZR2020MC077, ZR202111220001)
  • Shandong Key R&D Program (2018YFA0901702, TJYXZDXK-056B, 2019GSF107088, ZR2020MC077, ZR202111220001)
  • National Science Foundation of Shandong (2018YFA0901702, TJYXZDXK-056B, 2019GSF107088, ZR2020MC077, ZR202111220001)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords
SENP1, MRTF-A, SUMOylation, CYR61, CXCR4, mesenchymal stem cells, angiogenesis, cell migration, P300, histone acetylation, nuclear translocation, lysine residues, vascular regeneration

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