PreprintArticleVersion 1This version is not peer-reviewed
Integrative Multi-Omics Approach in Vascular Ehlers-Danlos Syndrome: Further Insights into the Disease Mechanisms by Proteomic Analysis of Patient Dermal Fibroblasts
Version 1
: Received: 4 November 2024 / Approved: 5 November 2024 / Online: 5 November 2024 (13:34:40 CET)
How to cite:
Chiarelli, N.; Cinquina, V.; Zoppi, N.; Bertini, V.; Maddaluno, M.; De Leonibus, C.; Settembre, C.; Venturini, M.; Colombi, M.; Ritelli, M. Integrative Multi-Omics Approach in Vascular Ehlers-Danlos Syndrome: Further Insights into the Disease Mechanisms by Proteomic Analysis of Patient Dermal Fibroblasts. Preprints2024, 2024110294. https://doi.org/10.20944/preprints202411.0294.v1
Chiarelli, N.; Cinquina, V.; Zoppi, N.; Bertini, V.; Maddaluno, M.; De Leonibus, C.; Settembre, C.; Venturini, M.; Colombi, M.; Ritelli, M. Integrative Multi-Omics Approach in Vascular Ehlers-Danlos Syndrome: Further Insights into the Disease Mechanisms by Proteomic Analysis of Patient Dermal Fibroblasts. Preprints 2024, 2024110294. https://doi.org/10.20944/preprints202411.0294.v1
Chiarelli, N.; Cinquina, V.; Zoppi, N.; Bertini, V.; Maddaluno, M.; De Leonibus, C.; Settembre, C.; Venturini, M.; Colombi, M.; Ritelli, M. Integrative Multi-Omics Approach in Vascular Ehlers-Danlos Syndrome: Further Insights into the Disease Mechanisms by Proteomic Analysis of Patient Dermal Fibroblasts. Preprints2024, 2024110294. https://doi.org/10.20944/preprints202411.0294.v1
APA Style
Chiarelli, N., Cinquina, V., Zoppi, N., Bertini, V., Maddaluno, M., De Leonibus, C., Settembre, C., Venturini, M., Colombi, M., & Ritelli, M. (2024). Integrative Multi-Omics Approach in Vascular Ehlers-Danlos Syndrome: Further Insights into the Disease Mechanisms by Proteomic Analysis of Patient Dermal Fibroblasts. Preprints. https://doi.org/10.20944/preprints202411.0294.v1
Chicago/Turabian Style
Chiarelli, N., Marina Colombi and Marco Ritelli. 2024 "Integrative Multi-Omics Approach in Vascular Ehlers-Danlos Syndrome: Further Insights into the Disease Mechanisms by Proteomic Analysis of Patient Dermal Fibroblasts" Preprints. https://doi.org/10.20944/preprints202411.0294.v1
Abstract
Dominant mutations in COL3A1 are known to cause vascular Ehlers-Danlos syndrome (vEDS) by impairing extracellular matrix (ECM) homeostasis. This disruption leads to the fragility of soft connective tissues and a significantly increased risk of life-threatening arterial and organ ruptures. Currently, treatments for vEDS are primarily symptomatic, largely due to a limited understanding of its underlying pathobiology and molecular mechanisms. In this study, we conducted a com-prehensive analysis of the intracellular proteome of vEDS fibroblasts, integrating these findings with our previous transcriptome results to identify key molecular pathways that drive the disease. Additionally, we explored the therapeutic potential of inhibiting miR-29b-3p as a proof of concept. Our integrative multi-omics analysis revealed complex pathological networks, emphasizing the critical role of miRNAs, particularly miR-29b-3p, in impairing ECM organization, autophagy, and cellular stress responses, all of which contribute to the pathogenesis of vEDS. Notably. the inhi-bition of miR-29b-3p in vEDS fibroblasts resulted in the upregulation of several differentially expressed target genes involved in these critical processes, as well as increased protein expression of essential ECM components, such as collagen types V and I. These changes suggest potential therapeutic benefits aimed at improving ECM integrity and restoring intracellular homeostasis. Overall, these insights not only enhance our understanding of the complex biological mechanisms underlying vEDS but also provide a solid foundation for future research focused on developing targeted treatment strategies to address this life-threatening disorder effectively.
Keywords
extracellular matrix; collagen type I; collagen type V; miR-29b; multi-omics approach; proteome; transcriptome; vascular Ehlers-Danlos syndrome
Subject
Biology and Life Sciences, Life Sciences
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
