Transforming growth factor‐β1 signalling triggers vascular endothelial growth factor resistance and monocyte dysfunction in type 2 diabetes mellitus

Makowski, Lena; Leffers, Merle; Waltenberger, Johannes; Pardali, Evangelia

doi:10.1111/jcmm.16543

Cited by 10 publications

(6 citation statements)

References 34 publications

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“…Although the evidence about the expression of Col I and VEGF in hyperglycemia-induced tendon damage is controversial, 23 , 71 , 81 , 82 our results are in line with the reduction of Col I and neoangiogenesis reported in preclinical and clinical settings of diabetic tendinopathy. 21 , 81 , 83 – 85 The TGF-β1 related effects in diabetes 51 , 74 , 81 , 86 – 89 on the levels of Col I, the main component of tendon dry mass 90 and of VEGF, the most important angiogenic factor involved in tendon healing, 91 support the potential role of TGF-β released by ASC-CM in improving tenocytes mediated tendon healing process under HG stimulus.…”

Section: Discussionmentioning

confidence: 86%

Effects of adipose-derived mesenchymal stem cell conditioned medium on human tenocytes exposed to high glucose

Trotta,

Itro,

Lepre

et al. 2024

Therapeutic Advances in Musculoskeletal

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Introduction: Diabetic tendinopathy is a common invalidating and challenging disease that may be treated using stem cells. However, the effects of adipose-derived mesenchymal stem cell conditioned medium (ASC-CM) in diabetic tendinopathy have never been explored. Objectives: The present study evaluated the effects of ASC-CM on morphology, cell viability, structure, and scratch wound closure of human tenocytes (HTNC) exposed to high glucose (HG). Design: Experimental study. Methods: HTNC were exposed to HG (25 mM) for 7, 14 and 21 days with or without ASC-CM for the last 24 h. CM was collected from 4 × 105 ASCs, centrifuged for 10 min at 200 g and sterilized with 0.22 μm syringe filter. Results: At 7 days, HG-HTNC had decreased cell viability [72 ± 2%, p < 0.01 versus normal glucose (NG)] compared to NG-HTNC (90 ± 5%). A further decrement was detected after 14 and 21 days (60 ± 4% and 60 ± 5%, both, p < 0.01 versus NG and p < 0.01 versus HG7). While NG-HTNC evidenced a normal fibroblast cell-like elongated morphology, HG-HTNC showed increased cell roundness. In contrast, HG-HTNC exposed to ASC-CM showed a significant increase in cell viability, an improved cell morphology and higher scratch wound closure at all HG time points. Moreover, the exposure to ASC-CM significantly increased thrombospondin 1 and transforming growth factor beta 1 (TGF-β1) content in HG-HTNC. The TGF-β1 elevation was paralleled by higher Collagen I and Vascular Endothelial Growth Factor in HG-HTNC. Conclusion: ASC-CM may restore the natural morphology, cell viability and structure of HTNC, promoting their scratch wound closure through TGF-β1 increase.

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Section: Discussionmentioning

confidence: 86%

Effects of adipose-derived mesenchymal stem cell conditioned medium on human tenocytes exposed to high glucose

Trotta,

Itro,

Lepre

et al. 2024

Therapeutic Advances in Musculoskeletal

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“…After the determination of mRNA expression, VEGFA, KDR, MAPK14, and PPARA were verified to be the effective targets. In T2DM patients, the expression of soluble VEGF-receptor 1 was increased in monocytes under high-glucose conditions, which inhibited VEGF signaling ( Makowski et al, 2021 ). VEGF resistance was a molecular concept that caused cellular dysfunction in diabetes mellitus ( Tchaikovski et al, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

Exploration of the hypoglycemic mechanism of Fuzhuan brick tea based on integrating global metabolomics and network pharmacology analysis

Xiang,

You,

Zeng

et al. 2024

Front. Mol. Biosci.

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Introduction: Fuzhuan brick tea (FBT) is a worldwide popular beverage which has the appreciable potential in regulating glycometabolism. However, the reports on the hypoglycemic mechanism of FBT remain limited.Methods: In this study, the hypoglycemic effect of FBT was evaluated in a pharmacological experiment based on Kunming mice. Global metabolomics and network pharmacology were combined to discover the potential target metabolites and genes. In addition, the real-time quantitative polymerase chain reaction (RT-qPCR) analysis was performed for verification.Results: Seven potential target metabolites and six potential target genes were screened using the integrated approach. After RT-qPCR analysis, it was found that the mRNA expression of VEGFA, KDR, MAPK14, and PPARA showed significant differences between normal and diabetes mellitus mice, with a retracement after FBT treatment.Conclusion: These results indicated that the hypoglycemic effect of FBT was associated with its anti-inflammatory activities and regulation of lipid metabolism disorders. The exploration of the hypoglycemic mechanism of FBT would be meaningful for its further application and development.

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“…T2DM leads to increased TGFβ signaling, which interferes with VEGFA-induced monocyte migration and leads to monocyte dysfunction. TGFβ signaling can affect monocyte function, causing vascular complications [ 43 ] in T2DM patients. Studies have found that serum TGF-β1 levels in patients with Alzheimer’s disease (AD), vascular dementia (VaD), and Parkinson’s disease dementia (PDD) are significantly increased, but serum TGF-β1 levels in AD and VaD are significantly higher than those in PDD [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Exploration and Clinical Verification of the Blood Co-Expression Genes of Type 2 Diabetes Mellitus and Mild Cognitive Dysfunction in the Elderly

et al. 2023

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With the development of society, the incidence of dementia and type 2 diabetes (T2DM) in the elderly has been increasing. Although the correlation between T2DM and mild cognitive impairment (MCI) has been confirmed in the previous literature, the interaction mechanism remains to be clarified. To explore the co-pathogenic genes in the blood of MCI and T2DM patients, clarify the correlation between T2DM and MCI, achieve the purpose of early disease prediction, and provide new ideas for the prevention and treatment of dementia. We downloaded T2DM and MCI microarray data from GEO databases and identified the differentially expressed genes associated with MCI and T2DM. We obtained co-expressed genes by intersecting differentially expressed genes. Then, we performed GO and KEGG enrichment analysis of co-DEGs. Next, we constructed the PPI network and found the hub genes in the network. By constructing the ROC curve of hub genes, the most valuable genes for diagnosis were obtained. Finally, the correlation between MCI and T2DM was clinically verified by means of a current situation investigation, and the hub gene was verified by qRT-PCR. A total of 214 co-DEGs were selected, 28 co-DEGs were up-regulated, and 90 co-DEGs were down-regulated. Functional enrichment analysis showed that co-DEGs were mainly enriched in metabolic diseases and some signaling pathways. The construction of the PPI network identified the hub genes in MCI and T2DM co-expression genes. We identified nine hub genes of co-DEGs, namely LNX2, BIRC6, ANKRD46, IRS1, TGFB1, APOA1, PSEN1, NPY, and ALDH2. Logistic regression analysis and person correlation analysis showed that T2DM was correlated with MCI, and T2DM increased the risk of cognitive impairment. The qRT-PCR results showed that the expressions of LNX2, BIRC6, ANKRD46, TGFB1, PSEN1, and ALDH2 were consistent with the results of bioinformatic analysis. This study screened the co-expressed genes of MCI and T2DM, which may provide new therapeutic targets for the diagnosis and treatment of diseases.

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Transforming growth factor‐β1 signalling triggers vascular endothelial growth factor resistance and monocyte dysfunction in type 2 diabetes mellitus

Cited by 10 publications

References 34 publications

Effects of adipose-derived mesenchymal stem cell conditioned medium on human tenocytes exposed to high glucose

Effects of adipose-derived mesenchymal stem cell conditioned medium on human tenocytes exposed to high glucose

Exploration of the hypoglycemic mechanism of Fuzhuan brick tea based on integrating global metabolomics and network pharmacology analysis

Exploration and Clinical Verification of the Blood Co-Expression Genes of Type 2 Diabetes Mellitus and Mild Cognitive Dysfunction in the Elderly

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