Dataset Information

Crosstalk between type 2 diabetic microenvironment and human adipose tissue- derived pericytes

ABSTRACT: Pericytes (PCs) are multipotent contractile cells that wrap around the endothelial cells to maintain the blood vessel's functionality and integrity. The hyperglycemia associated with Type 2 diabetes mellitus (T2DM) was shown to impair the function of PCs and increase the risk of diabetes complications. In this study, we aimed to investigate the deleterious effect of the diabetic microenvironment on the regenerative capacities of human PCs. PCs isolated from human adipose tissue were cultured in the presence or absence of serum collected from diabetic patients (DS). The functionality of PCs was analysed after 6, 14, and 30 days. Microscopic examination of PCs cultured in DS (DS-PCs) showed increased aggregate formation and altered surface topography with hyperbolic invaginations. Compared to PCs cultured in normal serum (NS-PCs), DS-PCs showed more fragmented mitochondria and thicker nuclear membrane. DS caused impaired angiogenic differentiation of PCs as confirmed by tube formation, decreased VEGF-A and IGF-1 gene expression, upregulated TSP1, PF4, actin related protein 2/3 complex and downregulated COL21A1 protein expression. These cells suffered higher apoptotis and showed higher expression of Clic4, apoptosis facilitator BCl-2-like protein serine/threonine protein phosphatase, and Caspase-7 proteins. DS-PCs showed dysregulated DNA repair genes CDKN1A, SIRT1, XRCC5 and TERF2 and up-regulation of the pro-inflammatory genes ICAM1, IL-6, and TNF-α. DS treated cells also showed disruption in the expression of the focal adhesion and binding proeins TSP1, TGF- β, fibronectin and PCDH7. DS-PCs showed resistance mechanisms upon exposure to diabetic microenvironment by maitining the intracellular ROS level and upregulation of ECM organizing proteins vinculin, IQGAP1, and tubulin beta chain.These data show that the diabetic microenvironment exert a deleterious effect on the regenerative capacities of human adipose tissue-derived PCs, and may thus have possible implications on the vascular complications of type-2 diabetes mellitus. Nevertheless, their protective mechanisms when initially exposed to DS could provide a promising cellular therapy for T2DM.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: sameh MAGDELDIN

LAB HEAD: Sameh Magdeldin

PROVIDER: PXD048187 | Pride | 2024-05-23

REPOSITORIES: Pride

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The cross talk between type II diabetic microenvironment and the regenerative capacities of human adipose tissue-derived pericytes: a promising cell therapy.

Ahmed Toka A TA Ahmed Sara M SM Elkhenany Hoda H El-Desouky Mohamed A MA Magdeldin Sameh S Osama Aya A Anwar Ali Mostafa AM Mohamed Ihab K IK Abdelgawad Mohamed Essameldin ME Hanna Demiana H DH El-Badri Nagwa N

Stem cell research & therapy 20240208 1

<h4>Background</h4>Pericytes (PCs) are multipotent contractile cells that wrap around the endothelial cells (ECs) to maintain the blood vessel's functionality and integrity. The hyperglycemia associated with Type 2 diabetes mellitus (T2DM) was shown to impair the function of PCs and increase the risk of diabetes complications. In this study, we aimed to investigate the deleterious effect of the diabetic microenvironment on the regenerative capacities of human PCs.<h4>Methods</h4>PCs isolated fro ...[more]

PMID: 38331889

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Project description:Skeletal muscle mitochondrial dysfunction is secondary to T2DM and can be improved by long-term regular exercise training Mitochondrial dysfunction has long been implicated to play a causative role in development of type 2 diabetes (T2DM). However, a growing number of recent studies provide data that mitochondrial dysfunction is a consequence of T2DM development. The aim of our study is to clarify in further detail the causal role of mitochondrial dysfunction in T2DM by a comprehensive ex vivo analysis of mitochondrial function combined with global gene expression analysis in muscle of pre-diabetic newly diagnosed untreated T2DM subjects and long-standing insulin treated T2DM subjects compared with age- and BMI-matched controls. In addition, we assessed the impact of long-term interval exercise training on physical activity performance, mitochondrial function and glycemic control in long-standing insulin-treated T2DM subjects. Ex vivo mitochondrial density, quality and functioning was comparable between pre-diabetic subjects and matched controls, however, gene expression analysis showed a switch from carbohydrate toward lipids as energy source in pre-diabetes subjects. In contrast, long-term insulin treated T2DM subjects had slightly decreased mitochondrial density and ex vivo function. Expression of Krebs cycle and OXPHOS related genes were decreased, indicating a decreased capacity to use lipids as an energy source. The insulin-treated T2DM subjects had a lower physical activity level than pre-diabetic and normoglycemic subjects. A 52 weeks exercise training of these subjects increased submaximal oxidative efficiency, increased in vivo PCr recovery rate, as well as mildly increased in vitro mitochondrial function. Gene expression of β-oxidation, Krebs cycle and OXPHOS-related genes was increased. Our data demonstrate that mitochondrial dysfunction is rather a consequence than a causative factor in T2DM development as it was only detected in overt diabetes and not in early diabetes. Regular exercise training stabilized exogenous insulin requirement and improved mitochondrial functioning, fatty acid oxidation and general physical work load capacity in long-standing insulin-treated T2DM subjects. As such, the present study shows for the first time that long-term exercise interventions are beneficial in this group of complex diabetes patient and may prevent further metabolic deterioration. Insulin-treated T2DM subjects before and after 52 weeks of exercise training (T2DM_0 and T2DM_52), normoglycemic controls (NGT) and pre-diabetes subjects (IGT) and were selected. RNA was extracted from skeletal muscle biopsies and hybridized on Affymetrix microarrays.

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	180923_DS1_14.mgf	Mgf
	180923_DS1_14.wiff	Wiff
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	180923_DS1_14_searchgui_out.zip	Other
	180923_DS1_30.mgf	Mgf