Glial cell line-derived neurotrophic factor induced the differentiation of amniotic fluid-derived stem cells into vascular endothelial-like cells in vitro

2015 ◽  
Vol 47 (1) ◽  
pp. 9-19 ◽  
Author(s):  
Ruyu Zhang ◽  
Ying Lu ◽  
Ju Li ◽  
Jia Wang ◽  
Caixia Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Amniotic Fluid ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Vascular Endothelial

scholarly journals Transplantation of Amniotic Fluid-Derived Stem Cells Preconditioned with Glial Cell Line-Derived Neurotrophic Factor Gene Alleviates Renal Fibrosis

2018 ◽  
Vol 28 (1) ◽  
pp. 65-78 ◽  
Author(s):  
Shulin Li ◽  
Yuan Zhao ◽  
Zhuojun Wang ◽  
Jia Wang ◽  
Caixia Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Growth Factor ◽  
Amniotic Fluid ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Interstitial Fibrosis ◽  
Renal Interstitial Fibrosis ◽  
Peritubular Capillaries

Amniotic fluid-derived stem cells (AFSCs), which exhibit both embryonic and mesenchymal stem cell characteristics, have been shown to mitigate the degree of renal interstitial fibrosis. The aim of the present study was to determine whether transplantation of glial cell line-derived neurotrophic factor (GDNF)–modified AFSCs is more useful than transplantation of unmodified AFSCs for the treatment of renal interstitial fibrosis. Mice were randomly assigned to a sham-operation group (sham), a unilateral ureteral obstruction (UUO)-saline solution group (UUO), an AFSC transplantation group (AFSC) and a GDNF-modified AFSC transplantation group (GDNF-AFSC) and sacrificed at days 3 and 7 post-surgery (six in each group). We showed that GDNF-AFSCs noticeably suppressed oxidative stress and inflammation; additionally, GDNF-AFSCs positively regulated peritubular capillaries (PTCs), vascular endothelial growth factor (VEGF), hypoxia inducible factor-1α (HIF-1α), and transforming growth factor-β1 (TGF-β1) protein levels. Transmission electron microscopy (TEM) revealed that mitochondrial injury induced by the UUO model was significantly ameliorated after the mice were treated with GDNF-AFSCs. Therefore, we determined that GDNF gene promotes the abilities of AFSCs to inhibit inflammatory and oxidative stress effects, repair renal microvessels, relieve tissue hypoxia and mitochondrial damage, and, ultimately, alleviate renal interstitial fibrosis.

scholarly journals The major determinant of the heparin binding of glial cell-line-derived neurotrophic factor is near the N-terminus and is dispensable for receptor binding

2007 ◽  
Vol 404 (1) ◽  
pp. 131-140 ◽  
Author(s):  
Ivan Alfano ◽  
Parvez Vora ◽  
Rosemary S. Mummery ◽  
Barbara Mulloy ◽  
Christopher C. Rider
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Transforming Growth Factor ◽  
Basic Amino Acid ◽  
Transforming Growth Factor Β ◽  
Heparin Binding ◽  
Binding Sequence

GDNF (glial cell-line-derived neurotrophic factor), and the closely related cytokines artemin and neurturin, bind strongly to heparin. Deletion of a basic amino-acid-rich sequence of 16 residues N-terminal to the first cysteine of the transforming growth factor β domain of GDNF results in a marked reduction in heparin binding, whereas removal of a neighbouring sequence, and replacement of pairs of other basic residues with alanine had no effect. The heparin-binding sequence is quite distinct from the binding site for the high affinity GDNF polypeptide receptor, GFRα1 (GDNF family receptor α1), and heparin-bound GDNF is able to bind GFRα1 simultaneously. The heparin-binding sequence of GDNF is dispensable both for GFRα1 binding, and for activity for in vitro neurite outgrowth assay. Surprisingly, the observed inhibition of GDNF bioactivity with the wild-type protein in this assay was still found with the deletion mutant lacking the heparin-binding sequence. Heparin neither inhibits nor potentiates GDNF–GFRα1 interaction, and the extracellular domain of GFRα1 does not bind to heparin itself, precluding heparin cross-bridging of cytokine and receptor polypeptides. The role of heparin and heparan sulfate in GDNF signalling remains unclear, but the present study indicates that it does not occur in the first step of the pathway, namely GDNF–GFRα1 engagement.

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