miR-PAIR: microRNA-protein analysis of integrative relationship for the identification of significantly working miRNAs.

MicroRNAs (miRNAs), which are small non-coding RNAs, are recognized as important significant endogenous bio-molecules that regulate the post-transcriptional processes of target genes. However, predictive methods for significantly working miRNAs are poorly understood. The present study aimed to establish a novel method, miRNA protein analysis of integrative relationship (miR-PAIR), for the identification of effectively working miRNAs involved in physiological or pathological events.

Evaluation of molecular interaction between intercellular lipid organization in human stratum corneum and terpenes using time-resolved synchrotron X-ray diffraction.

The stratum corneum (SC) presents certain limitations for topical administration of medication, which can be overcome using penetration enhancers (PEs) such as terpene (TP). The SC is also crucial for maintaining the skin barrier and consists of two lamellar structures: the short periodicity phase (SPP) and long periodicity phase (LPP). In this study, we monitored changes in the X-ray diffraction peaks of the human SC, 30 min after TP application (neroridol, 1,8-cineol, and d-limonene).

Abemaciclib-induced epithelial-mesenchymal transition mediated by cyclin-dependent kinase 4/6 independent of cell cycle arrest pathway.

Abemaciclib (ABM), a cyclin-dependent kinase 4/6 inhibitor, shows pharmacological effects in cell cycle arrest. Epithelial-mesenchymal transition is an important cellular event associated with pathophysiological states such as organ fibrosis and cancer progression. In the present study, we evaluated the contribution of factors associated with cell cycle arrest to ABM-induced epithelial-mesenchymal transition.

Anti-Helicobacter pylori activity of swertianolin, isolated from swertia herb.

Helicobacter pylori is a Gram-negative, spiral-shaped, motile bacterium present in human stomachs that causes gastric ulcers. A preliminary screening revealed that a methanolic extract of swertia herb demonstrated anti-H. pylori activity.

Role of integrin α2 in methotrexate-induced epithelial-mesenchymal transition in alveolar epithelial A549 cells.

Methotrexate (MTX) is widely used to treat various diseases. However, it induces adverse reactions like serious lung injury, including pulmonary fibrosis. Increasing evidence suggests that epithelial-mesenchymal transition (EMT) in injured alveolar epithelium contributes to the development of the pathophysiological state of the lung.

Role of Nrf2 in Methotrexate-Induced Epithelial-Mesenchymal Transition in Alveolar A549 Cells.

Methotrexate (MTX) is known to induce serious lung diseases, such as pulmonary fibrosis. Although we demonstrated that MTX is associated with epithelial-mesenchymal transition (EMT), the underlying mechanism remains unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2), an oxidative stress response regulator, is related to EMT induction.

Effect of Corticosteroids on Peptide Transporter 2 Function and Induction of Innate Immune Response by Bacterial Peptides in Alveolar Epithelial Cells.

In the lung alveolar region, the innate immune system serves as an important host defense system. We recently reported that peptide transporter 2 (PEPT2) has an essential role in the uptake of bacterial peptides and induction of innate immune response in alveolar epithelial cells. In this study, we aimed to clarify the effects of corticosteroids on PEPT2 function and PEPT2-dependent innate immune response.

Characterization of miR-34a-Induced Epithelial-Mesenchymal Transition in Non-Small Lung Cancer Cells Focusing on p53.

Background: Epithelial-mesenchymal transition (EMT), a phenotypic conversion of the epithelial to mesenchymal state, contributes to cancer progression. Currently, several microRNAs (miRNAs) are associated with EMT-mediated cancer progression, but the contribution of miR-34a to EMT in cancer cells remains controversial. The present study aimed to clarify the role of miR-34a in the EMT-related phenotypes of human non-small cell lung cancer (NSCLC) cell lines, A549 (p53 wild-type) and H1299 (p53-deficient).

Functional expression of equilibrative and concentrative nucleoside transporters in alveolar epithelial cells.

Equilibrative nucleoside transporters (ENTs) and concentrative nucleoside transporters (CNTs) mediate the cellular uptake of nucleosides and nucleobases across the plasma membrane and play important roles in the salvage pathways of nucleotide synthesis. However, information about nucleoside transport systems in the lung alveolar epithelial cells is limited. Therefore, in the present study, we examined the function and expression of nucleoside transporters using primary cultured alveolar type II cells and transdifferentiated type I-like cells.

Evaluation on epithelial-mesenchymal state and microRNAs focusing on isolated alveolar epithelial cells from bleomycin injured rat lung.

Several studies using bleomycin (BLM)-induced lung injury rat model revealed that epithelial-mesenchymal transition (EMT) contributes to pulmonary fibrosis. Conversely, microRNAs (miRNAs) are considered as useful markers of various diseases. In the present study, we aimed to characterize the EMT state through focusing on alveolar epithelial cells and identify the miRNAs that can be used as markers to predict pulmonary fibrosis using a BLM-induced lung injury rat model.

Differential mechanisms underlying methotrexate-induced cell death and epithelial-mesenchymal transition in A549 cells.

Epithelial-mesenchymal transition (EMT), a biological process through which epithelial cells transdifferentiate into mesenchymal cells, is involved in several pathological events, such as cancer progression and organ fibrosis. So far, we have found that methotrexate (MTX), an anticancer drug, induced EMT in the human A549 alveolar adenocarcinoma cell line. However, the relationship between EMT and the cytotoxicity induced by MTX remains unclear.

miR-484: A Possible Indicator of Drug-Induced Pulmonary Fibrosis.

Background: Drug-induced lung injury leads to serious lung diseases, such as pulmonary fibrosis. We demonstrated in an alveolar epithelial cell line A549/ABCA3 that certain microRNAs were associated with bleomycin induced epithelial-mesenchymal transition (EMT) which is closely related to pulmonary fibrosis. In this study, we focused on the role of miR-484 in drug-induced EMT using A549/ABCA3 cells and a mouse lung injury model.

Suppressive effect of quercetin against bleomycin-induced epithelial-mesenchymal transition in alveolar epithelial cells.

Quercetin is a flavonol that is known to have numerous beneficial biological effects such as an anti-fibrotic effect. Epithelial-mesenchymal transition (EMT) of alveolar type II epithelial cells is one of major causes of pulmonary fibrosis. However, the effect of quercetin on drug-induced EMT in alveolar type II cells is not known.

Transport of ribavirin in human myelogenous leukemia cell line K562.

The anticancer effect of ribavirin, a purine nucleoside analogue, has been studied using cultured cancer cells such as the human myelogenous leukemia cell line K562. In order to exert its pharmacological effect, ribavirin has to enter cancer cells. However, there is little information concerning the transport mechanism of ribavirin into K562 cells.

Role of plasminogen activator inhibitor-1 in methotrexate-induced epithelial-mesenchymal transition in alveolar epithelial A549 cells.

There is increasing evidence that epithelial-mesenchymal transition (EMT) contributes to the development of organ fibrosis. We demonstrated that methotrexate (MTX) clearly induced EMT through the transforming growth factor (TGF)-β-related signaling pathway in human alveolar epithelial cell line, A549. However, critical factors associated with MTX-induced EMT have not yet been identified.

Suppression of P-glycoprotein by cigarette smoke extract in human lung-derived A549/P-gp cells.

Effect of long-term treatment with cigarette smoke extract (CSE) on the function and expression of P-glycoprotein (P-gp) in lung alveolar epithelial cells was examined using A549/P-gp cell line expressing P-gp. CSE treatment suppressed P-gp activity in a concentration- and treatment time-dependent manner. The suppression of P-gp activity by CSE was irreversible for at least 96 h after removal of CSE.

Effect of transforming growth factor-β1 on functional expression of monocarboxylate transporter 1 in alveolar epithelial A549 cells.

Epithelial-mesenchymal transition (EMT) contributes to the development of severe lung diseases, such as pulmonary fibrosis. Recently, it has been reported that EMT involves complex metabolic reprogramming triggered by several factors including transforming growth factor (TGF-β1) and that monocarboxylate transporter (MCT1) plays an essential role in these metabolic changes. The aim of the present study was to clarify the functional expression of MCT1 during TGF-β1-induced EMT in alveolar epithelial A549 cells.

Anticancer Drug-Induced Epithelial-Mesenchymal Transition via p53/miR-34a axis in A549/ABCA3 Cells.

Purpose: Several anticancer drugs including bleomycin (BLM) and methotrexate (MTX) cause serious lung diseases such as pulmonary fibrosis. Although evidences showing the association of epithelial-mesenchymal transition (EMT) with pulmonary fibrosis are increasing, the mechanism underlying anticancer drug-induced EMT has been poorly understood. On the other hand, miR-34a, a non-coding small RNA, has been highlighted as a key factor to regulate EMT in lung.

Investigation on inhibitory effect of folic acid on methotrexate-induced epithelial-mesenchymal transition focusing on dihydrofolate reductase.

Use of methotrexate (MTX) can induce serious adverse lung reactions, such as pulmonary fibrosis. Recently, we demonstrated that the epithelial-mesenchymal transition (EMT), which triggers pulmonary fibrosis, was induced by MTX, and folic acid (FA) suppressed MTX-induced EMT in A549 cells. In this study, the role of dihydrofolate reductase (DHFR), a target of MTX, in FA-mediated inhibition of MTX-induced EMT was evaluated.

Association of cell cycle arrest with anticancer drug-induced epithelial-mesenchymal transition in alveolar epithelial cells.

Many drugs exert serious cytotoxic effects on pulmonary tissues. Although several reports have shown an association of epithelial-mesenchymal transition (EMT) with anticancer drug-induced lung injury, mechanisms of these effects are poorly understood. In the present study, we evaluated mechanisms of anticancer drug-induced EMT, with a focus on involvement of cell cycle arrest.

Role of peptide transporter 2 and MAPK signaling pathways in the innate immune response induced by bacterial peptides in alveolar epithelial cells.

Aims: The innate immune response induced by bacterial peptidoglycan peptides, such as γ-d-glutamyl-meso-diaminopimelic acid (iE-DAP), is an important host defense system. However, little is known about the innate immune response in the lung alveolar region. In this study, we examined induction of the innate immune response by iE-DAP in human alveolar epithelial cell lines, NCI-H441 (H441) and A549.

Functional expression of breast cancer resistance protein and cholesterol effect in human erythrocyte membranes.

In human erythrocyte membranes, various influx and efflux transporters are functionally expressed. However, their transport characteristics and modulation under disease states are not fully understood. In this study, we first examined the expression and detailed transport characteristics of breast cancer resistance protein (BCRP), an efflux ABC transporter, using inside-out membrane vesicles (IOVs) prepared from human erythrocytes, and then studied the effect of membrane cholesterol on BCRP function.

Reduced folate carrier-mediated methotrexate transport in human distal lung epithelial NCl-H441 cells.

Objectives: We had previously found that reduced folate carrier (RFC; SLC19A1) is mainly involved in an influx of transport of methotrexate (MTX), a folate analogue, using alveolar epithelial A549 cells. Therefore, we examined MTX uptake in NCl-H441 (H441) cells, another in vitro alveolar epithelial model, focusing on the localization of RFC in the present study.

Methods: Transport function of RFC in H441 cells was studied using [ H]MTX.

Transport of AOPP-Albumin into Human Alveolar Epithelial A549 Cell.

Purpose: Alveolar clearance of proteins, such as albumin, plays an essential role in recovery from lung injuries. Albumin is known to be oxidized by reactive oxygen species (ROS), leading to generation of advanced oxidation protein products (AOPP)-albumin in the alveolar lining fluid. In this study, we aimed to characterize the uptake of FITC-labeled AOPP-albumin (FITC-AOPP-albumin) into human alveolar epithelial cell line, A549.

Folic acid prevents methotrexate-induced epithelial-mesenchymal transition via suppression of secreted factors from the human alveolar epithelial cell line A549.

Methotrexate (MTX) often induces serious lung diseases such as pulmonary fibrosis. Although MTX is known to be a folic acid (FA) antagonist, the effect of FA on MTX-induced lung injury remains unclear. Recent studies indicate that epithelial-mesenchymal transition (EMT) is involved in pulmonary fibrosis.