Transcriptomic and computational analysis identified LPA metabolism, KLHL14 and KCNE3 as novel regulators of Epithelial-Mesenchymal Transition

Lollo, Valeria Di; Canciello, Angelo; Orsini, Massimiliano; Bernabò, Nicola; Ancora, Massimo; Federico, Marta Di; Curini, Valentina; Mattioli, Mauro; Russo, Valentina; Mauro, Annunziata; Cammà, Cesare; Barboni, Barbara

doi:10.1038/s41598-020-61017-y

Cited by 13 publications

(20 citation statements)

References 80 publications

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“…This enzyme is not a specific marker for foetal hepatocytes, since it is present both in hepatoblasts, in hepatocyte-like cells obtained in vitro by hESC differentiation [ 60 ], and in mature hepatocytes [ 61 , 62 ]. Furthermore, it is thought that analysis of changes in GSTA1 gene expression may be useful in assessing the progression of EMT, during which it may increase [ 63 ]; however, we did not observe either at the mRNA or protein levels.…”

Section: Discussioncontrasting

confidence: 82%

In Vitro Differentiation of Human Amniotic Epithelial Cells into Hepatocyte-like Cells

Michalik

Wieczorek

Czekaj

2022

Cells

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Human amniotic epithelial cells (hAECs) represent an interesting clinical alternative to human embryonic (hESCs) and induced pluripotent (hiPSCs) stem cells in regenerative medicine. The potential of hAECs can be enhanced ex vivo by their partial pre-differentiation. The aim of this study was to evaluate the effectiveness of 18-day differentiation of hAECs into endodermal cells, hepatic precursor cells, and cells showing functional features of hepatocytes using culture media supplemented with high (100 ng/mL) concentrations of EGF or HGF. The cells obtained after differentiation showed changes in morphology and increased expression of AFP, ALB, CYP3A4, CYP3A7, and GSTP1 genes. HGF was more effective than EGF in increasing the expression of liver-specific genes in hAECs. However, EGF stimulated the differentiation process more efficiently and yielded more hepatocyte-like cells capable of synthesizing α-fetoprotein during differentiation. Additionally, after 18 days, GST transferases, albumin, and CYP P450s, which proved their partial functionality, were expressed. In summary, HGF and EGF at a dose of 100 ng/mL can be successfully used to obtain hepatocyte-like cells between days 7 and 18 of hAEC differentiation. However, the effectiveness of this process is lower compared with hiPSC differentiation; therefore, optimization of the composition of the medium requires further research.

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Section: Discussioncontrasting

confidence: 82%

In Vitro Differentiation of Human Amniotic Epithelial Cells into Hepatocyte-like Cells

Michalik

Wieczorek

Czekaj

2022

Cells

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“…Moreover, oAECs acquired a tenogenic phenotype as they organized themselves in 3D tendon-like structures [184]. Tendon differentiation occurred with a stepwise process confirmed by the fact that oAEC expressed mesenchymal markers after co-culture, such as α-SMA, which they did not possess when initially harvested [174,184,185,191,192].…”

Section: Comparative Studies With Growth Factorsmentioning

confidence: 97%

“…AECs could be well suited to develop an understanding of the efficiency of tendon induction techniques as they lack mesenchymal and tenogenic markers when harvested but acquire them through the differentiation process [184,188,191,192].…”

Section: Stem Cellsmentioning

confidence: 99%

In Vitro Innovation of Tendon Tissue Engineering Strategies

Citeroni

Ciardulli

Russo

et al. 2020

IJMS

Self Cite

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Tendinopathy is the term used to refer to tendon disorders. Spontaneous adult tendon healing results in scar tissue formation and fibrosis with suboptimal biomechanical properties, often resulting in poor and painful mobility. The biomechanical properties of the tissue are negatively affected. Adult tendons have a limited natural healing capacity, and often respond poorly to current treatments that frequently are focused on exercise, drug delivery, and surgical procedures. Therefore, it is of great importance to identify key molecular and cellular processes involved in the progression of tendinopathies to develop effective therapeutic strategies and drive the tissue toward regeneration. To treat tendon diseases and support tendon regeneration, cell-based therapy as well as tissue engineering approaches are considered options, though none can yet be considered conclusive in their reproduction of a safe and successful long-term solution for full microarchitecture and biomechanical tissue recovery. In vitro differentiation techniques are not yet fully validated. This review aims to compare different available tendon in vitro differentiation strategies to clarify the state of art regarding the differentiation process.

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“…Recently, Lollo also pointed out that GSTM3 acted as a key epithelial–mesenchymal transition inducer operating in amniotic epithelial cells using RNA sequencing. 37 …”

Section: The Role Of Gstm3 In Cancersmentioning

confidence: 99%

<p>GSTM3 Function and Polymorphism in Cancer: Emerging but Promising</p>

Wang¹,

Yang²,

You³

et al. 2020

CMAR

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Cancer is a major cause of human mortality; however, the molecular mechanisms and proteomic biomarkers that cause tumor progression in malignant tumors are either unknown or only partially revealed. Glutathione S-transferases mu3 (GSTM3), which belongs to a family of xenobiotic detoxifying phase II enzymes, is associated with carcinogen detoxification and the metabolism of exogenous electrophilic substances. It has been reported that GSTM3 has different polymorphisms in various tumor cells and regulates tumorigenesis, cell invasion, metastasis, chemoresistance, and oxidative stress. Deep research into the regulatory mechanisms involved in disorders of GSTM3 expression and the function of GSTM3 in different cancers may facilitate improvements in cancer prevention and targeted therapy. The combination of GSTM3 with other family members can regulate the carcinogenesis and susceptibility to different cancers in humans. GSTM3 also regulates the reactive oxygen species (ROS) and participates in oxidative stress-mediated pathology. Here, we provide a general introduction to GSTM3 in order to better understand the role of GSTM3 in cancer.

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Transcriptomic and computational analysis identified LPA metabolism, KLHL14 and KCNE3 as novel regulators of Epithelial-Mesenchymal Transition

Cited by 13 publications

References 80 publications

In Vitro Differentiation of Human Amniotic Epithelial Cells into Hepatocyte-like Cells

In Vitro Differentiation of Human Amniotic Epithelial Cells into Hepatocyte-like Cells

In Vitro Innovation of Tendon Tissue Engineering Strategies

<p>GSTM3 Function and Polymorphism in Cancer: Emerging but Promising</p>

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