Biology subjects

Marchetti-Deschmann, M.

Publications and source records attributed to Marchetti-Deschmann, M..

3 recordsLinked to original sources

bioRxiv2024

Unravelling the glycome in human intervertebral disc degeneration: Aberrant glycosylation modulates inflammation and metabolism.

Intervertebral disc (IVD) degeneration is one of the major contributing causes of low back pain (LBP), a common health issue that imposes a significant socio-economic burden on society. Previous work has demonstrated a dysregulated glycome in animal models of IVD degeneration; however, the role of glycosylation in pathogenesis is unknown. The objective of this study was to characterise altered glycan expression in IVD degeneration and elucidate the functional role of this response. Glycans in human healthy (n=6) and degenerated IVD (n=6) were examined through UPLC-MS and MALDI-IMS. These findings were correlated with proteomic analysis by LC-MS and functional in vitro studies using RNA sequencing. IVD degeneration was associated with a hypersialylated N-glycome, predominantly -2,6 linked sialic acid. Confirming hypersialylation, we investigated sialylations functional role through mechanistic studies using a sialylation inhibitor (3Fax-peracetyl Neu5Ac). Sialylation inhibition in vitro modulated inflammatory and metabolic pathways, demonstrating a functional role for glycosylation in IVD degeneration. Brief summaryIVD degeneration is associated with altered glycosylation, a potential target for new therapies.

bioengineering↗

bioRxiv2022

Changes in Tissue Protein N-Glycosylation and Associated Molecular Signature Occur in the Human Parkinsonian Brain in a Region-Specific Manner

Parkinsons Disease (PD) associated state of neuroinflammation due to the aggregation of aberrant proteins is widely reported. One type of post-translational modification involved in protein stability is glycosylation. Here, we aimed to characterise the human Parkinsonian nigro-striatal N-glycome, and related transcriptome/proteome, and its correlation with endoplasmic reticulum stress and unfolded protein response (UPR), providing a comprehensive characterisation of the PD molecular signature. Significant changes were seen upon PD: 3% increase in sialylation and 5% increase in fucosylation in both regions, and 2% increase in oligomannosylated N-glycans in the substantia nigra. In the latter, a decrease in the mRNA expression of sialidases and an upregulation in the UPR pathway were also seen. To show the correlation between these, we also describe an in vitro functional study where changes in specific glycosylation trait enzymes (inhibition of sialyltransferases) led to impairments in cell mitochondrial activity, changes in glyco-profile and upregulation in UPR pathways. This complete characterisation of the human nigro-striatal N-glycome provides an insight into the glycomic profile of PD through a transversal approach while combining the other PD "omics" pieces, which can potentially assist in the development of glyco-focused therapeutics.

neuroscience↗

bioRxiv2020

Temporal Changes Guided by Mesenchymal Stem Cells on a 3D Microgel Platform Enhances Angiogenesis In Vivo at a Low-Cell Dose

Therapeutic factors secreted by mesenchymal stem cells (MSCs) promote angiogenesis in vivo. However, delivery of MSCs in the absence of a cytoprotective environment offers limited efficacy due to low cell retention, poor graft survival and the non-maintenance of a physiologically relevant dose of growth factors at the injury site. The delivery of stem cells on an extracellular matrix (ECM)-based platform alters cell behaviour including migration, proliferation and paracrine activity, which are essential for angiogenesis. We demonstrate the biophysical and biochemical effects of pre-conditioning human MSCs for 96 hours on a three-dimensional ECM-based microgel platform. By altering the macromolecular concentration surrounding cells in the microgels, the pro-angiogenic phenotype of hMSCs can be tuned in a controlled manner through cell-driven changes in extracellular stiffness and outside-in integrin signaling. The microgels tested at a low-cell dose (5x104 cells) in a pre-clinical hindlimb ischemia model showed accelerated formation of new blood vessels with a reduced inflammatory response impeding progression of tissue damage. Molecular analysis revealed that several key mediators of angiogenesis were upregulated in the low-cell dose microgel group, providing a mechanistic insight of pathways modulated in vivo. Our research adds to current knowledge in cell encapsulation strategies by highlighting the importance of preconditioning or priming the capacity of biomaterials through cell-material interactions. Obtaining therapeutic efficacy at a low-cell dose in the microgel platform is a promising clinical route that would aid faster tissue repair and reperfusion in no-option patients suffering from peripheral arterial diseases such as Critical Limb Ischemia (CLI).

bioengineering↗