scholarly journals Dual role of RACK1 in airway epithelial mesenchymal transition and apoptosis

2020 ◽  
Vol 24 (6) ◽  
pp. 3656-3668 ◽  
Author(s):  
Yue Pu ◽  
Yuan‐qi Liu ◽  
Yan Zhou ◽  
Yi‐fan Qi ◽  
Shi‐ping Liao ◽  
...  
2020 ◽  
Vol 11 ◽  
Author(s):  
Melissa Skibba ◽  
Adam Drelich ◽  
Michael Poellmann ◽  
Seungpyo Hong ◽  
Allan R. Brasier

Idiopathic Pulmonary Fibrosis (IPF) is a chronically progressive interstitial lung that affects over 3 M people worldwide and rising in incidence. With a median survival of 2–3 years, IPF is consequently associated with high morbidity, mortality, and healthcare burden. Although two antifibrotic therapies, pirfenidone and nintedanib, are approved for human use, these agents reduce the rate of decline of pulmonary function but are not curative and do not reverse established fibrosis. In this review, we discuss the prevailing epithelial injury hypothesis, wherein pathogenic airway epithelial cell-state changes known as Epithelial Mesenchymal Transition (EMT) promotes the expansion of myofibroblast populations. Myofibroblasts are principal components of extracellular matrix production that result in airspace loss and mortality. We review the epigenetic transition driving EMT, a process produced by changes in histone acetylation regulating mesenchymal gene expression programs. This mechanistic work has focused on the central role of bromodomain-containing protein 4 in mediating EMT and myofibroblast transition and initial preclinical work has provided evidence of efficacy. As nanomedicine presents a promising approach to enhancing the efficacy of such anti-IPF agents, we then focus on the state of nanomedicine formulations for inhalable delivery in the treatment of pulmonary diseases, including liposomes, polymeric nanoparticles (NPs), inorganic NPs, and exosomes. These nanoscale agents potentially provide unique properties to existing pulmonary therapeutics, including controlled release, reduced systemic toxicity, and combination delivery. NP-based approaches for pulmonary delivery thus offer substantial promise to modify epigenetic regulators of EMT and advance treatments for IPF.


2018 ◽  
Vol 8 (1) ◽  
pp. 62 ◽  
Author(s):  
Julianna Maria Santos ◽  
Fazle Hussain

Background: Reduced levels of magnesium can cause several diseases and increase cancer risk. Motivated by magnesium chloride’s (MgCl2) non-toxicity, physiological importance, and beneficial clinical applications, we studied its action mechanism and possible mechanical, molecular, and physiological effects in prostate cancer with different metastatic potentials.Methods: We examined the effects of MgCl2, after 24 and 48 hours, on apoptosis, cell migration, expression of epithelial mesenchymal transition (EMT) markers, and V-H+-ATPase, myosin II (NMII) and the transcription factor NF Kappa B (NFkB) expressions.Results: MgCl2 induces apoptosis, and significantly decreases migration speed in cancer cells with different metastatic potentials.  MgCl2 reduces the expression of V-H+-ATPase and myosin II that facilitates invasion and metastasis, suppresses the expression of vimentin and increases expression of E-cadherin, suggesting a role of MgCl2 in reversing the EMT. MgCl2 also significantly increases the chromatin condensation and decreases NFkB expression.Conclusions: These results suggest a promising preventive and therapeutic role of MgCl2 for prostate cancer. Further studies should explore extending MgCl2 therapy to in vivo studies and other cancer types.Keywords: Magnesium chloride, prostate cancer, migration speed, V-H+-ATPase, and EMT.


2020 ◽  
Vol 20 ◽  
Author(s):  
Qionghui Wu ◽  
Haidong Wei ◽  
Wenbo Meng ◽  
Xiaodong Xie ◽  
Zhenchang Zhang ◽  
...  

: Annexin, a calcium-dependent phospholipid binding protein, can affect tumor cell adhesion, proliferation, apoptosis, invasion and metastasis, as well as tumor neovascularization in different ways. Recent studies have shown that annexin exists not only as an intracellular protein in tumor cells, but also in different ways to be secret outside the cell as a “crosstalk” tool for tumor cells and tumor microenvironment, thus playing an important role in the development of tumors, such as participating in epithelial-mesenchymal transition, regulating immune cell behavior, promoting neovascularization and so on. The mechanism of annexin secretion in the form of extracellular vesicles and its specific role is still unclear. This paper summarizes the main role of annexin secreted into the extracellular space in the form of extracellular vesicles in tumorigenesis and drug resistance and analyzes its possible mechanism.


2020 ◽  
Vol 81 (1) ◽  
Author(s):  
Lina A. Aeshra ◽  
Maiada Moustafa ◽  
Mohammed I. Y. Elmallah ◽  
Said Abdelrahman Salih ◽  
Ibrahim Y. Abdel Kader

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