Advanced glycation end products cause increased CCN family and extracellular matrix gene expression in the diabetic rodent retina

AbstractDebilitating cases of tendon pain and degeneration affect the majority of diabetic individuals. The high rate of tendon degeneration persists even when glucose levels are well controlled, suggesting that other mechanisms may drive tendon degeneration in diabetic patients. The purpose of this study was to investigate the impact of advanced glycation end-products on tendon fibroblasts to further our mechanistic understanding of the development and progression of diabetic tendinopathy. We proposed that advanced glycation end-products would induce limitations to mitochondrial function and proliferative capacity in tendon-derived fibroblasts, restricting their ability to maintain biosynthesis of tendon extracellular matrix. Using an in-vitro cell culture system, rat Achilles tendon fibroblasts were treated with glycolaldehyde-derived advanced glycation end-products (0, 50, 100, and 200μg/ml) for 48 hours in normal glucose (5.5mM) and high glucose (25mM) conditions. We demonstrate that tendon fibroblasts treated with advanced glycation end-products display reduced ATP production, electron transport efficiency, and proliferative capacity. These impairments were coupled with alterations in mitochondrial DNA content and expression of genes associated with extracellular matrix remodeling, mitochondrial energy metabolism, and apoptosis. Our findings suggest that advanced glycation end-products disrupt tendon fibroblast homeostasis and may be involved in the development and progression of diabetic tendinopathy.

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ADVANCED GLYCATION END PRODUCTS (AGES): IS THE SCIENTIFIC NEED TO TRAVEL BACK IN TIME TO REGAIN HEALTH NOW OBVIOUS?

10.36106/ijar/5108208 ◽

2021 ◽

pp. 20-22

Author(s):

Pradeep Kumar Radhakrishnan ◽

Roshini Ambat ◽

Gayathri Ananyajyothi Ambat ◽

Bindu R Nayar ◽

Y A Nazer

Keyword(s):

Extracellular Matrix ◽

Advanced Glycation End Products ◽

Target Genes ◽

Cell Types ◽

Nuclear Factor Κb ◽

Cooking Methods ◽

Advanced Glycation ◽

Surface Receptors ◽

Glycation End Products ◽

End Products

Advanced glycation end products (AGEs) are proteins or lipids that become glycated after exposure to sugars. AGEs may modify the extracellular matrix (ECM); modify the action of hormones, cytokines, and free radicals via engagement of cell surface receptors; and impact the function of intracellular proteins..AGEs block nitric oxide activity in the endothelium and cause the production of reactive oxygen species. AGEs cause microvascular and macrovascular complications by formation of cross-links between molecules in the basement membrane of the extracellular matrix and by engaging the receptor for advanced glycation end products (RAGE). Activation of RAGE by AGEs causes upregulation of the transcription factor nuclear factor-κB and its target genes. AGEs can be formed either endogenously or exogenously. Endogenously, advanced glycation takes place in all cell types via the Maillard reaction between reducing sugars and amino residues present in proteins, lipids, and DNA, resulting in loss of protein structure and function followed in some instances by cellular apoptosis. Transition to plant based antioxidant diet with traditional Indian cooking methods seems to confer multitude of health benets.

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Upregulation of mesangial growth factor and extracellular matrix synthesis by advanced glycation end products via a receptor-mediated mechanism

Diabetes ◽

10.2337/diabetes.46.11.1881 ◽

1997 ◽

Vol 46 (11) ◽

pp. 1881-1887 ◽

Cited By ~ 25

Author(s):

G. Pugliese ◽

F. Pricci ◽

G. Romeo ◽

F. Pugliese ◽

P. Mene ◽

...

Keyword(s):

Extracellular Matrix ◽

Growth Factor ◽

Advanced Glycation End Products ◽

Advanced Glycation ◽

Matrix Synthesis ◽

Glycation End Products ◽

End Products

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Advanced Glycation End Products Inhibit Production and Activity of Matrix Metalloproteinase-2 in Human Umbilical Vein Endothelial Cells

Journal of International Medical Research ◽

10.1177/147323000703500517 ◽

2007 ◽

Vol 35 (5) ◽

pp. 709-715 ◽

Cited By ~ 8

Author(s):

L Gao ◽

L Kang ◽

Q Chen ◽

C Chen ◽

B Xu ◽

...

Keyword(s):

Gene Expression ◽

Endothelial Cells ◽

Conditioned Medium ◽

Advanced Glycation End Products ◽

Umbilical Vein ◽

Advanced Glycation ◽

Glycation End Products ◽

End Products ◽

Umbilical Vein Endothelial Cells ◽

Expression And Activity

The aim of this study was to investigate the effects of advanced glycation end products (AGEs) on the expression and activity of matrix metalloproteinases-2 (MMP-2) in human umbilical vein endothelial cells (HUVECs). Cultured HUVECs were incubated with various concentrations of AGEs-modified albumin or unmodified albumin for different time periods. Protein and gene expression of MMP-2 and the receptor for AGEs (RAGE) were measured by Western blot and reverse transcription-polymerase chain reaction, respectively. The activity of MMP-2 in the conditioned medium was measured by gelatin zymography. The AGE-modified albumin inhibited MMP-2 but increased RAGE protein and gene expression in HUVECs in a concentration- and time-dependent manner. An inhibition of MMP-2 activity was also detected in the conditioned medium of HUVECs incubated with AGEs-modified albumin. In conclusion, AGEs inhibited the expression and activity of MMP-2 in HUVECs; this may be mediated through upregulation of RAGE.

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