scholarly journals Non-cell-autonomous manner of AAV administration to attenuate cardiomyocyte hypertrophy by targeting paracrine signaling on ECM to reduce viral dosage

2022 ◽  
Vol 7 (1) ◽  
Author(s):  
Lei Liu ◽  
Peng Yue ◽  
Yue Zhang ◽  
Yimin Hua ◽  
Wenwei Bi ◽  
...  
2014 ◽  
Author(s):  
Jolanta Gutkowska ◽  
Ahmed Menouar ◽  
Marek Jankowski

2013 ◽  
Vol 100 (3) ◽  
pp. S23
Author(s):  
M. Pavone ◽  
S. Malpani ◽  
M. Dyson ◽  
D. Monsivais ◽  
N. Mittal ◽  
...  

Oncogene ◽  
2021 ◽  
Vol 40 (11) ◽  
pp. 1957-1973
Author(s):  
Hyunho Yoon ◽  
Chih-Min Tang ◽  
Sudeep Banerjee ◽  
Mayra Yebra ◽  
Sangkyu Noh ◽  
...  

AbstractTargeted therapies for gastrointestinal stromal tumor (GIST) are modestly effective, but GIST cannot be cured with single agent tyrosine kinase inhibitors. In this study, we sought to identify new therapeutic targets in GIST by investigating the tumor microenvironment. Here, we identified a paracrine signaling network by which cancer-associated fibroblasts (CAFs) drive GIST growth and metastasis. Specifically, CAFs isolated from human tumors were found to produce high levels of platelet-derived growth factor C (PDGFC), which activated PDGFC-PDGFRA signal transduction in GIST cells that regulated the expression of SLUG, an epithelial-mesenchymal transition (EMT) transcription factor and downstream target of PDGFRA signaling. Together, this paracrine induce signal transduction cascade promoted tumor growth and metastasis in vivo. Moreover, in metastatic GIST patients, SLUG expression positively correlated with tumor size and mitotic index. Given that CAF paracrine signaling modulated GIST biology, we directly targeted CAFs with a dual PI3K/mTOR inhibitor, which synergized with imatinib to increase tumor cell killing and in vivo disease response. Taken together, we identified a previously unappreciated cellular target for GIST therapy in order to improve disease control and cure rates.


2021 ◽  
Vol 22 (15) ◽  
pp. 7931
Author(s):  
Ning Liu ◽  
Shiqiang Sun ◽  
Pengjie Wang ◽  
Yanan Sun ◽  
Qingjuan Hu ◽  
...  

Serotonin, also known as 5-hydroxytryptamine (5-HT), is a metabolite of tryptophan and is reported to modulate the development and neurogenesis of the enteric nervous system, gut motility, secretion, inflammation, sensation, and epithelial development. Approximately 95% of 5-HT in the body is synthesized and secreted by enterochromaffin (EC) cells, the most common type of neuroendocrine cells in the gastrointestinal (GI) tract, through sensing signals from the intestinal lumen and the circulatory system. Gut microbiota, nutrients, and hormones are the main factors that play a vital role in regulating 5-HT secretion by EC cells. Apart from being an important neurotransmitter and a paracrine signaling molecule in the gut, gut-derived 5-HT was also shown to exert other biological functions (in autism and depression) far beyond the gut. Moreover, studies conducted on the regulation of 5-HT in the immune system demonstrated that 5-HT exerts anti-inflammatory and proinflammatory effects on the gut by binding to different receptors under intestinal inflammatory conditions. Understanding the regulatory mechanisms through which 5-HT participates in cell metabolism and physiology can provide potential therapeutic strategies for treating intestinal diseases. Herein, we review recent evidence to recapitulate the mechanisms of synthesis, secretion, regulation, and biofunction of 5-HT to improve the nutrition and health of humans.


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