scholarly journals The effect of inhibiting exosomes derived from adipose-derived stem cells via the TGF-β1/Smad pathway on the fibrosis of keloid fibroblasts

Gland Surgery ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 1046-1056
Author(s):  
Zhi-Yuan Wu ◽  
Hui-Jun Zhang ◽  
Zhi-Hong Zhou ◽  
Zhan-Peng Li ◽  
Si-Mu Liao ◽  
...  
2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Zetao Chen ◽  
Yihong Chen ◽  
Yan Li ◽  
Weidong Lian ◽  
Kehong Zheng ◽  
...  

AbstractGlioma is one of the most lethal cancers with highly vascularized networks and growing evidences have identified glioma stem cells (GSCs) to account for excessive angiogenesis in glioma. Aberrant expression of paired-related homeobox1 (Prrx1) has been functionally associated with cancer stem cells including GSCs. In this study, Prrx1 was found to be markedly upregulated in glioma specimens and elevated Prrx1 expression was inversely correlated with prognosis of glioma patients. Prrx1 potentiated stemness acquisition in non-stem tumor cells (NSTCs) and stemness maintenance in GSCs, accompanied with increased expression of stemness markers such as SOX2. Prrx1 also promoted glioma angiogenesis by upregulating proangiogenic factors such as VEGF. Consistently, silencing Prrx1 markedly inhibited glioma proliferation, stemness, and angiogenesis in vivo. Using a combination of subcellular proteomics and in vitro analyses, we revealed that Prrx1 directly bound to the promoter regions of TGF-β1 gene, upregulated TGF-β1 expression, and ultimately activated the TGF-β/smad pathway. Silencing TGF-β1 mitigated the malignant behaviors induced by Prrx1. Activation of this pathway cooperates with Prrx1 to upregulate the expression of stemness-related genes and proangiogenic factors. In summary, our findings revealed that Prrx1/TGF-β/smad signal axis exerted a critical role in glioma stemness and angiogeneis. Disrupting the function of this signal axis might represent a new therapeutic strategy in glioma patients.


2007 ◽  
Vol 40 (6) ◽  
pp. 809-823 ◽  
Author(s):  
A. T. Mehlhorn ◽  
P. Niemeyer ◽  
K. Kaschte ◽  
L. Muller ◽  
G. Finkenzeller ◽  
...  

2011 ◽  
Vol 7 (12) ◽  
pp. 1457-1473 ◽  
Author(s):  
Alan Yan ◽  
Tomer Avraham ◽  
Jamie C Zampell ◽  
Yosef S Haviv ◽  
Evan Weitman ◽  
...  

2021 ◽  
Author(s):  
Xuling Lv ◽  
Hao Chen ◽  
Zikai Zhang ◽  
Tian Li ◽  
Qing Wei ◽  
...  

Abstract Background: Pelvic floor dysfunction (PFD) is a spectrum of disorders including stress urinary incontinence and pelvic organ prolapse. Transforming growth factor-β1 (TGF-β1) can induce mesenchymal stem cells (MSCs) to differentiate into smooth muscle cells (SMCs). SMCs derived from adipose-derived stem cells (ADSCs) can be used to repair damaged pelvic floor smooth muscle tissues, which is of great interest for clinical applications using stem cell therapy for PFD. The Wnt/β-catenin pathway acts as a decisive factor in the fate of stem cells.Methods and Results: In this study, we used medium containing TGF-β1, TGF-β1 inhibitor LY2109761, or Wnt/β-catenin inhibitor KYA1797K, to induce ADCSs to differentiate into SMCs in vitro to explore the influence of TGF-β1 on the myogenic differentiation of ADCSs via the Wnt/β-catenin pathway. Results: 1) TGF-β1 induces ADSC-derived SMCs to hyper-express the SMC markers including SMA-α, Desmin, Calponin, and SMMHC ; 2) TGF-β1 activates the Wnt/β-catenin signaling pathway in ADSCs. After blocking TGF-β1, the Wnt/β-catenin pathway and myogenic differentiation in cells were inhibited; 3) the Wnt/β-catenin pathway is involved in the differentiation of ADSCs into SMCs. After differentiation induction, the synchronized changes in the activation of Wnt/β-catenin signaling and the expression of SMC-specific proteins showed a trend of simultaneous changes, and after the inhibition of the Wnt pathway, the adult muscle differentiation was significantly inhibited.Conclusions: We established a simpler and more efficient method for inducing ADSCs to differentiate into SMCs using TGF-β1 and demonstrated that the Wnt/β-catenin signaling pathway is activated during this process.


Life Sciences ◽  
2019 ◽  
Vol 232 ◽  
pp. 116637 ◽  
Author(s):  
Yangang Zhang ◽  
Chuantao Cheng ◽  
Shuang Wang ◽  
Meifeng Xu ◽  
Dewu Zhang ◽  
...  

2018 ◽  
Vol 370 (2) ◽  
pp. 708-717 ◽  
Author(s):  
Yu-Chi Wang ◽  
Rong-Fu Chen ◽  
Gerald Brandacher ◽  
W.P. Andrew Lee ◽  
Yur-Ren Kuo

2016 ◽  
Vol 105 (3) ◽  
pp. 900-911 ◽  
Author(s):  
Raimundo Romero ◽  
John K. Travers ◽  
Emilie Asbury ◽  
Attie Pennybaker ◽  
Laura Chubb ◽  
...  

2021 ◽  
Author(s):  
Jiong Zhou ◽  
Ji-Yang Shen ◽  
Li-En Tao ◽  
Huan Chen

Abstract Background: Keloids represent the dysregulation of cutaneous wound healing caused by aberrant fibroblast activities. Adipose-derived stem cells have been recognized as a promising treatment for keloids. However, their molecular mechanisms have not been fully elucidated. Methods: Skin biopsies were obtained from 10 keloid patients and 9 healthy volunteers. Fibroblasts isolated from all samples were divided into 2 groups, one co-cultured with adipose-derived stem cells, the other growing independently. Between each group, we compared the wound healing rate, fibroblasts’ survival rate, apoptosis rates, mRNA expressions and protein level of Col-1, Col-3, CTGF, P-4-HB. Results: In our research, no significant differences between normal fibroblasts and keloid fibroblasts in terms of wound-healing rate, survival rate, or apoptosis rate were found at the baseline. Adipose-derived stem cells strongly suppressed keloid fibroblasts’ proliferative and invasive behavior, but negatively regulated keloid fibroblast apoptosis. The further measurement of key components in keloid formation showed that adipose-derived stem cells upregulated Col-3 and CTGF levels in normal fibroblasts but downregulated protein expression of CTGF and P-4-HB in keloid fibroblasts. Conclusions: Adipose-derived stem cells had the potential to serve as a promising alternative for keloid treatment.


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