scholarly journals Suppression of transforming growth factor beta and vascular endothelial growth factor in diabetic nephropathy in rats by a novel advanced glycation end product inhibitor, OPB-9195

Diabetologia ◽  
1999 ◽  
Vol 42 (5) ◽  
pp. 579-588 ◽  
Author(s):  
K. Tsuchida ◽  
Z. Makita ◽  
S. Yamagishi ◽  
T. Atsumi ◽  
H. Miyoshi ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Vascular Endothelial ◽  
Advanced Glycation ◽  
Advanced Glycation End Product ◽  
Growth Factor Beta ◽  
Endothelial Growth Factor

scholarly journals LTBP4 affects renal fibrosis by influencing angiogenesis and altering mitochondrial structure

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Chi-Ting Su ◽  
Tzu-Ming Jao ◽  
Zsolt Urban ◽  
Yue-Jhu Huang ◽  
Daniel H. W. See ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Mitochondrial Morphology ◽  
Vascular Endothelial ◽  
Mitochondrial Structure ◽  
Growth Factor Beta ◽  
Endothelial Growth Factor

AbstractTransforming growth factor beta (TGFβ) signalling regulates extracellular matrix accumulation known to be essential for the pathogenesis of renal fibrosis; latent transforming growth factor beta binding protein 4 (LTBP4) is an important regulator of TGFβ activity. To date, the regulation of LTBP4 in renal fibrosis remains unknown. Herein, we report that LTBP4 is upregulated in patients with chronic kidney disease and fibrotic mice kidneys created by unilateral ureteral obstruction (UUO). Mice lacking the short LTBP4 isoform (Ltbp4S−/−) exhibited aggravated tubular interstitial fibrosis (TIF) after UUO, indicating that LTBP4 potentially protects against TIF. Transcriptomic analysis of human proximal tubule cells overexpressing LTBP4 revealed that LTBP4 influences angiogenic pathways; moreover, these cells preserved better mitochondrial respiratory functions and expressed higher vascular endothelial growth factor A (VEGFA) compared to wild-type cells under hypoxia. Results of the tube formation assay revealed that additional LTBP4 in human umbilical vein endothelial cell supernatant stimulates angiogenesis with upregulated vascular endothelial growth factor receptors (VEGFRs). In vivo, aberrant angiogenesis, abnormal mitochondrial morphology and enhanced oxidative stress were observed in Ltbp4S−/− mice after UUO. These results reveal novel molecular functions of LTBP4 stimulating angiogenesis and potentially impacting mitochondrial structure and function. Collectively, our findings indicate that LTBP4 protects against disease progression and may be of therapeutic use in renal fibrosis.

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