Related Experiment Video
Updated: Aug 4, 2026

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
Published on: August 3, 2018
Glucose stimulation of transforming growth factor-beta bioactivity in mesangial cells is mediated by thrombospondin-1
M H Poczatek1, C Hugo, V Darley-Usmar
1Department of Pathology, Division of Molecular and Cellular Pathology, and The Cell Adhesion and Matrix Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Abstract:
Glucose is a key factor in the development of diabetic complications, including diabetic nephropathy. The development of diabetic glomerulosclerosis is dependent on the fibrogenic growth factor, transforming growth factor-beta (TGF-beta). Previously we showed that thrombospondin-1 (TSP-1) activates latent TGF-beta both in vitro and in vivo. Activation occurs as the result of specific interactions of latent TGF-beta with TSP-1, which potentially alter the conformation of latent TGF-beta. As glucose also up-regulates TSP-1 expression, we hypothesized that the increased TGF-beta bioactivity observed in rat and human mesangial cells cultured with high glucose concentrations is the result of latent TGF-beta activation by autocrine TSP-1. Glucose-induced bioactivity of TGF-beta in mesangial cell cultures was reduced to basal levels by peptides from two different sequences that antagonize activation of latent TGF-beta by TSP, but not by the plasmin inhibitor, aprotinin. Furthermore, glucose-dependent stimulation of matrix protein synthesis was inhibited by these antagonist peptides. These studies demonstrate that glucose stimulation of TGF-beta activity and the resultant matrix protein synthesis are dependent on the action of autocrine TSP-1 to convert latent TGF-beta to its biologically active form. These data suggest that antagonists of TSP-dependent TGF-beta activation may be the basis of novel therapeutic approaches for ameliorating diabetic renal fibrosis.
More Related Videos
06:54Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
07:05TGF-β-mediated Endothelial to Mesenchymal Transition (EndMT) and the Functional Assessment of EndMT Effectors using CRISPR/Cas9 Gene Editing
Published on: February 26, 2021
Related Concept Videos
Cell Specific Gene Expression
Regulation of Angiogenesis and Blood Supply
TGF - β Signaling Pathway
cAMP-dependent Protein Kinase Pathways
Intracellular Signaling Affects Focal Adhesions
Some...
Hormones Regulating Blood Glucose
In addition to accelerating glucose uptake and utilization, insulin has...