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Cited by 19Hippo pathway signaling and YAP/TAZCongenital heart defects researchCardiovascular Function and Risk Factors

Elevated MST1 leads to apoptosis via depletion of YAP1 in cardiomyocytes exposed to high glucose

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Su, Dongmei, Li, Yanhua, Guan, Lina, Li, Qian, Shi, Cuige, Ma, Xu, Song, Yonghui·2021·Molecular Medicine
DOI 10.1186/s10020-021-00267-6PMC PMC7874454

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Abstract

BACKGROUND: Gestational diabetes mellitus is a risk factor for congenital heart defects. The article aimed to investigate the expression and roles of MST1, YAP1, Last1/2 and Survivin in modulating HG-induced cardiomyocyte apoptosis and maternal diabetes-induced heart abnormality. METHODS: Diabetes mellitus was induced in rats using streptozotocin. The protein expression and phosphorylation analysis in fetal heart tissue was assessed by western blot and immunohistochemical staining. Hoechst 33342 staining assay was performed to explore H9C2 apoptosis. The gene and protein expression in H9C2 cells was assessed by quantitative PCR and western blot. Knockdown of gene expression was assessed by RNA interference. RESULTS: Our results revealed that increased MST1 protein levels in the heart tissues of the offspring of diabetic rats in vivo and in H9C2 cardiomyocytes under HG treatment in vitro, respectively. Knockdown and overexpression experiments showed that MST1 played a key role in mediating HG-induced apoptosis in cardiomyocytes. Downregulation of YAP1 was associated with HG-induced, MST1-mediated cardiomyocyte apoptosis. Further study showed that MST1 downregulated the protein level of YAP1 through mediation of YAP1 phosphorylation on Ser127 and Ser397; this process also required LATS1/2 participation. MST1 overexpression increased the phosphorylation levels of LATS1/2, which were also shown to be increased in the heart tissues of diabetic offspring. We also found that YAP1 mediated the expression of Survivin during HG-induced apoptosis, and the Survivin-inhibitor YM155 partially inhibited the role of YAP1 in suppressing apoptosis induced by HG in cardiomyocytes. CONCLUSION: These findings reveal a regulatory mechanism of MST1/YAP1/Survivin signaling in modulating cardiomyocyte apoptosis in vitro and maternal diabetes-induced congenital heart defects in vivo.

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  • STZ-induced diabetes during pregnancy stimulates cardiomyocyte apoptosis in the offspring heart via activation of MST1 and downregulation of YAP1 and Survivin.

    “STZ-induced diabetes during pregnancy was also found to stimulate cardiomyocyte apoptosis in the offspring heart via activation of MST1 and downregulation of YAP1 and Survivin [122].”

    From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [122]

    The Methods describe streptozotocin-induced diabetes in pregnant rats, and the Results report increased MST1 and decreased YAP1 in fetal hearts. However, the apoptosis experiments and the finding of decreased Survivin were in high-glucose-treated cardiomyocytes in vitro; the Abstract Conclusion distinguishes those experiments from the in vivo findings on offspring heart defects. The claim presents the full apoptosis pathway, including Survivin downregulation, as demonstrated in offspring hearts. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • STZ-induced diabetes during pregnancy stimulates cardiomyocyte apoptosis in the offspring heart.

    “STZ-induced diabetes during pregnancy was also found to stimulate cardiomyocyte apoptosis in the offspring heart via activation of MST1 and downregulation of YAP1 and Survivin [122].”

    From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [122]

    The Materials and methods section describes streptozotocin-induced diabetes in pregnant rats, and the Results report increased MST1 and decreased YAP1 in fetal hearts. The Discussion reports MST1-dependent cardiomyocyte apoptosis after high-glucose exposure in vitro, but the paper does not show that apoptosis occurred in the offspring hearts or establish the proposed MST1–YAP1–Survivin mechanism there. (LLM, conf=0.86)

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Research works printed but not linked: 32

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Authors
Su, D., Li, Y., Guan, L., Li, Q., Shi, C., Ma, X., & Song, Y.
Affiliations
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
  • Linyi People's Hospital (CN)
Corresponding author
Ma, Xu
ORCID
Venue
Molecular Medicine
Publisher
Springer Science and Business Media LLC
Published
2021-02-10
Volume
27
Issue
1
Pages
13-13
ISSN
  • 1076-1551 (ISSN-L)
  • 1528-3658
DOI
10.1186/s10020-021-00267-6
PMC
PMC7874454
OpenAlex
W3128752743
Cited by
19
References
36
Citations by year
2026: 2 · 2025: 5 · 2024: 7 · 2023: 2 · 2022: 3
FWCI
1.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Medicine (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • the Non-profit Central Research Institute Fund of National Research Institute For Family Planing (Grant No. 2020GJZ01)
  • the National Natural Science Foundation of China (Grant No. 31871391)
  • the National Key Research and Development Program of China (Grant No. 2016 YFC1000307, YCZYPT[2018])
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
Keywords
MST1, YAP, cardiomyocyte apoptosis, high glucose, gestational diabetes mellitus, congenital heart disease, LATS1/2, survivin, YM155, YAP1 phosphorylation, maternal diabetes, fetal heart, H9c2 cells
MeSH terms
Survivin, YAP-Signaling Proteins, Hippo Kinases, Animals, Cell Line, Diabetes Mellitus, Experimental, Disease Models, Animal, Glucose, Imidazoles, Naphthoquinones, Phosphorylation, Streptozocin, Down-Regulation, Apoptosis, Protein Serine-Threonine Kinases, Myocytes, Cardiac, Intracellular Signaling Peptides and Proteins, Rats

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