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  • Clinical Research Article
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Overexpression of miR-22-3p and miR-29c-3p in CFU-Hill colonies is related to senescence process among children with low birth weight

Abstract

Background

The current study mainly focused on provide further insights into the association of the miR-22-3p and miR-29c-3p expression in CFU-Hill colonies with birth weight and senescence process in children.

Methods

This cross-sectional study evaluated 61 children (32 boys, 29 girls). The CFU-Hill colonies number was evaluated in vitro by cell culture technique and senescence was detected by β-galactosidase (SA-β-Gal) assay. Expression of miR-22-3p and miR-29c-3p isolated from CFU-Hill colonies were detected using quantitative real-time polymerase chain reaction.

Results

Birth weight was correlated with both CFU-Hill colonies and %SA-β-Gal positive staining. Multivariate linear regression analysis revealed that the senescence was a predictor of the lower CFU-Hill colonies number, while only the birth weight was a predictor of senescence of CFU-Hill colonies. Overexpression of miR-22-3p and miR-29c-3p was observed in CFU-Hill colonies isolated from children with low birth weight (LBW). Interestingly, we found a significant correlation between %SA-β-Gal cells staining positive for both miR-22-3p and miR-29c-3p.

Conclusion

The LBW is associated with decreased CFU-Hill colonies number and high senescence of these cells. The overexpression of miR-22-3p and miR-29c-3p may be partially responsible for this alteration due to regulation of several pathways related to the senescence process.

Impact

  • The study establishes a significant correlation between birth weight and the number of CFU-Hill colonies, suggesting that birth weight could be a predictive biomarker for vascular health in children.

  • Data indicates that cellular senescence is a predictor of reduced CFU-Hill colony numbers. This suggests that the aging process of these cells could be an important factor in understanding the vascular health issues in children with low birth weight.

  • The overexpression of miR-22-3p and miR-29c-3p in children with low birth weight and their correlation with increased cellular senescence highlight these microRNAs as possible molecular mechanisms influencing the aging of CFU-Hill colonies.

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Fig. 1: Association between birth weight, CFU-Hill colonies, and senescence process.
Fig. 2: Expression of miR-22-3p and its association with CFU-Hill colonies and senescence process.
Fig. 3: Expression of miR-29c-3p and its association with CFU-Hill colonies and senescence process.
Fig. 4: Kyoto encyclopedia of genes and genomes pathways with their P values.

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Data availability

The data underlying this study will be shared on reasonable request to the corresponding author.

References

  1. Liang, J. et al. Association between birth weight and risk of cardiovascular disease: Evidence from UK Biobank. NMCD 31, 2637–2643 (2021).

    PubMed  Google Scholar 

  2. Franco, M. C., Christofalo, D. M., Sawaya, A. L., Ajzen, S. A. & Sesso, R. Effects of low birth weight in 8- to 13-year-old children: implications in endothelial function and uric acid levels. Hypertension 48, 45–50 (2006).

    Article  CAS  PubMed  Google Scholar 

  3. Norman, M. Low birth weight and the developing vascular tree: a systematic review. Acta Paediatrica 97, 1165–1172 (2008).

    Article  PubMed  Google Scholar 

  4. Urbich, C. & Dimmeler, S. Endothelial progenitor cells: characterization and role in vascular biology. Circ. Res. 95, 343–353 (2004).

    Article  CAS  PubMed  Google Scholar 

  5. Balaji, S., King, A., Crombleholme, T. M. & Keswani, S. G. The Role of Endothelial Progenitor Cells in Postnatal Vasculogenesis: Implications for Therapeutic Neovascularization and Wound Healing. Adv. Wound Care 2, 283–295 (2013).

    Article  Google Scholar 

  6. Hill, J. M. et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N. Engl. J. Med. 348, 593–600 (2003).

    Article  PubMed  Google Scholar 

  7. Medina, R. J. et al. Endothelial Progenitors: A Consensus Statement on Nomenclature. Stem cells Transl. Med. 6, 1316–1320 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ligi, I. et al. A switch toward angiostatic gene expression impairs the angiogenic properties of endothelial progenitor cells in low birth weight preterm infants. Blood 118, 1699–1709 (2011).

    Article  CAS  PubMed  Google Scholar 

  9. Ligi, I. et al. Altered angiogenesis in low birth weight individuals: a role for anti-angiogenic circulating factors. J. Matern. Fetal Neon. Med. 27, 233–238 (2014).

    Article  ADS  CAS  Google Scholar 

  10. Souza, L. V. et al. Detrimental Impact of Low Birth Weight on Circulating Number and Functional Capacity of Endothelial Progenitor Cells in Healthy Children: Role of Angiogenic Factors. J. Pediatr. 206, 72–77 (2019).

    Article  CAS  PubMed  Google Scholar 

  11. Salazar-Martinez, E., Rodriguez-Valentin, R., Albavera-Hernandez, C., Carreon-Rodriguez, A. & Lazcano-Ponce, E. Number of colony-forming unit-Hill colonies among children and teenagers with obesity, dyslipidemia and breastfeeding history. NMCD 26, 534–540 (2016).

    CAS  PubMed  Google Scholar 

  12. Vassallo, P. F. et al. Accelerated senescence of cord blood endothelial progenitor cells in premature neonates is driven by SIRT1 decreased expression. Blood 123, 2116–2126 (2014).

    Article  CAS  PubMed  Google Scholar 

  13. Simoncini, S. et al. Biogenesis of Pro-senescent Microparticles by Endothelial Colony Forming Cells from Premature Neonates is driven by SIRT1-Dependent Epigenetic Regulation of MKK6. Sci. Rep. 7, 8277 (2017).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  14. Nikolajevic, J. et al. The Role of MicroRNAs in Endothelial Cell Senescence. Cells 11, 1185 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Krol, J., Loedige, I. & Filipowicz, W. The Widespread Regulation of microRNA Biogenesis, Function and Decay. Nat. Rev. Genet. 11, 597–610 (2010).

    Article  CAS  PubMed  Google Scholar 

  16. Liang, H. et al. miR-22-3p Suppresses Endothelial Progenitor Cell Proliferation and Migration via Inhibiting Onecut 1 (OC1)/Vascular Endothelial Growth Factor A (VEGFA) Signaling Pathway and Its Clinical Significance in Venous Thrombosis. Med. Sci. Monit. 26, e925482 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zhou, C. et al. Preeclampsia Downregulates MicroRNAs in Fetal Endothelial Cells: Roles of miR-29a/c-3p in Endothelial Function. J. Clin. Endocrinol. Metab. 102, 3470–3479 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  18. de Onis, M. et al. Development of a WHO growth reference for school-aged children and adolescents. Bull. W. Health Organ. 85, 660–667 (2007).

    Article  Google Scholar 

  19. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114, 1–22 (2004).

    Google Scholar 

  20. Kumari, R. & Jat, P. Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype. Front. Cell. Dev. Biol. 9, 645593 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lu, Q. & Rounds, S. Focal adhesion kinase and endothelial cell apoptosis. Microvasc. Res. 83, 56–63 (2012).

    Article  CAS  PubMed  Google Scholar 

  22. Bent, E. H., Gilbert, L. A. & Hemann, M. T. A senescence secretory switch mediated by PI3K/AKT/mTOR activation controls chemoprotective endothelial secretory responses. Gen. Dev. 30, 1811–1821 (2016).

    Article  CAS  Google Scholar 

  23. Del Re, D. P., Miyamoto, S. & Brown, J. H. Focal adhesion kinase as a RhoA-activable signaling scaffold mediating Akt activation and cardiomyocyte protection. J. Biol. Chem. 283, 35622–35629 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Liu, D. & Xu, Y. p53, oxidative stress, and aging. Antioxid. Red. Sign. 15, 1669–1678 (2011).

    Article  CAS  Google Scholar 

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Funding

This study was funded by a project grant from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (N°. 2015/20082-7) (N°. 2018/04013-3). Franco MC receives a research grant from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (N° 302879/2019-6) and CAPES-PRINT (N°. 88881.310737/2018-01).

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Contributions

P.R.P.S., F.T., L.V.S. and C.L.F. contributed to the investigation, acquisition, analysis, or interpretation of data for the work, and drafted the manuscript. M.C.F. contributed to the conceptualization, data curation, supervision, funding acquisition, project administration, and writing—review & editing. All authors critically revised the manuscript, gave final approval, and agreed to be accountable for all aspects of work ensuring integrity and accuracy.

Corresponding author

Correspondence to Maria do Carmo Franco.

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The authors declare no competing interests.

Ethics approval and consent to participate

This study was approved by the Research Ethics Committee of the Federal University of São Paulo (approval number: 3.318.000). Written informed consent was obtained from all parents or guardians, while written assent was obtained from all children.

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Souza, P.R.P., Thomazini, F., Souza, L.V. et al. Overexpression of miR-22-3p and miR-29c-3p in CFU-Hill colonies is related to senescence process among children with low birth weight. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03128-0

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