Vitiligo patient-derived keratinocytes exhibit characteristics of normal wound healing via epithelial to mesenchymal transition

2015 ◽  
Vol 24 (5) ◽  
pp. 391-393 ◽  
Author(s):  
Poulomi Banerjee ◽  
Sandhyaa Venkatachalam ◽  
Murali Krishna Mamidi ◽  
Ramesh Bhonde ◽  
Krupa Shankar ◽  
...  
2021 ◽  
Vol 22 (4) ◽  
pp. 1700
Author(s):  
Jihye Seo ◽  
Jain Ha ◽  
Eunjeong Kang ◽  
Haelim Yoon ◽  
Sewoong Lee ◽  
...  

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is a leading cause of cancer-related deaths. As HCC has a high mortality rate and its incidence is increasing worldwide, understanding and treating HCC are crucial for resolving major public health concerns. In the present study, wound healing screening assays were performed using natural product libraries to identify natural chemicals that can inhibit cancer cell migration. Glaucarubinone (GCB) showed a high potential for inhibiting cell migration. The anti-cancer effects of GCB were evaluated using the HCC cell line, Huh7. GCB showed anti-cancer effects, as verified by wound healing, cell migration, invasion, colony formation, and three-dimensional spheroid invasion assays. In addition, cells treated with GCB showed suppressed matrix metalloproteinase activities. Immunoblotting analyses of intracellular signaling pathways revealed that GCB regulated the levels of Twist1, a crucial transcription factor associated with epithelial-to-mesenchymal transition, and mitogen-activated protein kinase. The invasive ability of cancer cells was found to be decreased by the regulation of Twist1 protein levels. Furthermore, GCB downregulated phosphorylation of extracellular signal-regulated kinase. These results indicate that GCB exhibits anti-metastatic properties in Huh7 cells, suggesting that it could be used to treat HCC.


2018 ◽  
Vol 13 (5) ◽  
pp. 659-668 ◽  
Author(s):  
Sara Lovisa ◽  
Giannicola Genovese ◽  
Silvio Danese

Abstract Intestinal fibrosis is an inevitable complication in patients with inflammatory bowel disease [IBD], occurring in its two major clinical manifestations: ulcerative colitis and Crohn’s disease. Fibrosis represents the final outcome of the host reaction to persistent inflammation, which triggers a prolonged wound healing response resulting in the excessive deposition of extracellular matrix, eventually leading to intestinal dysfunction. The process of epithelial-to-mesenchymal transition [EMT] represents an embryonic program relaunched during wound healing, fibrosis and cancer. Here we discuss the initial observations and the most recent findings highlighting the role of EMT in IBD-associated intestinal fibrosis and fistulae formation. In addition, we briefly review knowledge on the cognate process of endothelial-to-mesenchymal transition [EndMT]. Understanding EMT functionality and the molecular mechanisms underlying the activation of this mesenchymal programme will permit designing new therapeutic strategies to halt the fibrogenic response in the intestine.


2021 ◽  
Vol 22 (17) ◽  
pp. 9280
Author(s):  
Hilal Arnouk ◽  
Gloria Yum ◽  
Dean Shah

Cripto-1 is an essential protein for human development that plays a key role in the early phase of gastrulation in the differentiation of an embryo as well as assists with wound healing processes. Importantly, Cripto-1 induces epithelial to mesenchymal transition to turn fixed epithelial cells into a more mobile mesenchymal phenotype through the downregulation of epithelial adhesion molecules such as E-cadherin, occludins, and claudins, and the upregulation of mesenchymal, mobile proteins, such as N-cadherin, Snail, and Slug. Consequently, Cripto-1’s role in inducing EMT to promote cell motility is beneficial in embryogenesis, but detrimental in the formation, progression and metastasis of malignant tumors. Indeed, Cripto-1 is found to be upregulated in most cancers, such as breast, lung, gastrointestinal, hepatic, renal, cervical, ovarian, prostate, and skin cancers. Through its role in EMT, Cripto-1 can remodel cancer cells to enable them to travel through the extracellular matrix as well as blood and lymphatic vessels to metastasize to different organs. Additionally, Cripto-1 promotes the survival of cancer stem cells, which can lead to relapse in cancer patients.


2018 ◽  
Vol 47 (10) ◽  
pp. 2463-2471 ◽  
Author(s):  
Abid Nordin ◽  
Shiplu Roy Chowdhury ◽  
Aminuddin Saim ◽  
Ruszymah Hj Idrus

2022 ◽  
Vol 2022 ◽  
pp. 1-23
Author(s):  
Yan Shi ◽  
Shang Wang ◽  
Ronghua Yang ◽  
Zhenmin Wang ◽  
Weiwei Zhang ◽  
...  

We previously showed that wound-induced hypoxia is related to keratinocyte migration. The ability of keratinocytes within wound healing to undergo epithelial to mesenchymal transition (EMT) contributes significantly to the acquisition of migratory properties. However, the effect of hypoxia on keratinocyte EMT on wound healing and the potential mechanism are poorly documented. This study first demonstrated that reactive oxygen species (ROS) appear to be an essential signalling mediator in keratinocytes with increased EMT and migration subjected to hypoxic conditions. Next, we showed that the expression of sex-determining region Y-box 2 (SOX2), a stemness-associated molecule, is ROS-dependent under hypoxia and that SOX2 inhibition in keratinocytes dramatically prevented hypoxia-induced EMT and migration. In addition, β-catenin was found to be a potential molecular target of SOX2, and the activation of Wnt/β-catenin was required for hypoxia-induced EMT and migration. Using an in vitro skin culture model and an in vivo skin wound model, our study further reinforced the critical role of ROS in inducing EMT through SOX2 expression and subsequent activation of Wnt/β-catenin, allowing for rapid reepithelialization of the wound area. Taken together, our findings reveal a previously unknown mechanism by which hypoxia promotes wound healing by promoting reepithelialization through the production of ROS, inducing keratinocyte EMT and migration via the enhancement of SOX2 and activation of Wnt/β-catenin.


Author(s):  
Matthew Futterman ◽  
Evan A. Zamir

It is increasingly clear that (collective) migration of epithelia plays an important role in morphogenesis and wound healing [6]. One of the interesting phenomena about epithelial migration is that the leading edge of the epithelia displays characteristics of both epithelia and cells undergoing EMT (epithelial-to-mesenchymal transition), so-called “partial” EMT. Developmental models in Drosophila and zebrafish have become important for studying signaling pathways involved in epithelial migration in recent years, but it is difficult to study the biomechanics of these systems. [2] Here, we revisit a little-used developmental model originally characterized by Chernoff [3] over two decades ago, which uses the area opaca (AO) of the chick embryo, an extraembryonic epithelium in birds which normally functions to spread across and encompass the nutritive yolk in a process called epiboly. We believe this model will be useful for studying epithelial migration because it is easily accessible and can be separated from the embryo to control the biomechanical environment.


Author(s):  
Abid Nordin ◽  
Haziq Kamal ◽  
Muhammad Dain Yazid ◽  
Aminuddin Saim ◽  
Ruszymah Idrus

Abstract Background Nigella sativa or commonly known as black seed or black cumin is one of the most ubiquitous complementary medicine. Epithelial to mesenchymal transition (EMT) of type 2 is defined by the balance between wound healing and tissue fibrosis, which is dependent to the state of inflammation. This systematic review is conducted to provide an overview regarding the reported effect of Nigella sativa and its bioactive compound on the type 2 EMT. Methods A search was done in EBSCOHOST, OVID and SCOPUS database to obtain potentially relevant articles that were published between 1823 and August 2019. This review includes studies that focus on the effect of Nigella sativa and its bioactive compound on the events related to type 2 EMT. Results A total of 1393 research articles were found to be potentially related to the effect of Nigella sativa and its bioactive compound, thymoquinone on Type 2 EMT. After screening was done, 22 research articles met inclusion criteria and were included in this review. Majority of the studies, reported better wound healing rate or significant prevention of tissue inflammation and organ fibrosis following Nigella sativa or thymoquinone treatments. In terms of wound healing, studies included reported progression of EMT related pathological changes after treatment with Nigella sativa or thymoquinone. Alternatively, in terms of fibrosis and inflammation, studies included reported reversal of pathological changes related to EMT after treatment with Nigella sativa or thymoquinone. Conclusion Through this review, Nigella sativa and thymoquinone have been associated with events in Type 2 EMT. They have been shown to promote wound healing, attenuate tissue inflammation, and prevent organ fibrosis via regulation of the EMT process.


2017 ◽  
Vol 18 ◽  
pp. 8-20 ◽  
Author(s):  
Abid Nordin ◽  
Nur Qisya Afifah Veronica Sainik ◽  
Mohamed S. Zulfarina ◽  
Isa Naina-Mohamed ◽  
Aminuddin Saim ◽  
...  

2021 ◽  
Vol 10 (11) ◽  
pp. 2403
Author(s):  
Laura Bornes ◽  
Guillaume Belthier ◽  
Jacco van Rheenen

Epithelial-to-mesenchymal transition (EMT) is a cellular program which leads to cells losing epithelial features, including cell polarity, cell–cell adhesion and attachment to the basement membrane, while gaining mesenchymal characteristics, such as invasive properties and stemness. This program is involved in embryogenesis, wound healing and cancer progression. Over the years, the role of EMT in cancer progression has been heavily debated, and the requirement of this process in metastasis even has been disputed. In this review, we discuss previous discrepancies in the light of recent findings on EMT, plasticity and hybrid E/M states. Moreover, we highlight various tumor microenvironmental cues and cell intrinsic signaling pathways that induce and sustain EMT programs, plasticity and hybrid E/M states. Lastly, we discuss how recent findings on plasticity, especially on those that enable cells to switch between hybrid E/M states, have changed our understanding on the role of EMT in cancer metastasis, stemness and therapy resistance.


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