Interplay between RAGE, CD44, and focal adhesion molecules in epithelial-mesenchymal transition of alveolar epithelial cells.

نویسندگان

  • Stephen T Buckley
  • Carlos Medina
  • Michael Kasper
  • Carsten Ehrhardt
چکیده

Fibrosis of the lung is characterized by the accumulation of myofibroblasts, a key mediator in the fibrogenic reaction. Cumulative evidence indicates that epithelial-mesenchymal transition (EMT), a process whereby epithelial cells become mesenchyme-like, is an important contributing source for the myofibroblast population. Underlying this phenotypical change is a dramatic alteration in cellular structure. The receptor for advanced glycation end-products (RAGE) has been suggested to maintain lung homeostasis by mediating cell adhesion, while the family of ezrin/radixin/moesin (ERM) proteins, on the other hand, serve as an important cross-linker between the plasma membrane and cytoskeleton. In the present investigation, we tested the hypothesis that RAGE and ERM interact and play a key role in regulating EMT-associated structural changes in alveolar epithelial cells. Exposure of A549 cells to inflammatory cytokines resulted in phosphorylation and redistribution of ERM to the cell periphery and localization with EMT-related actin stress fibers. Simultaneously, blockade of Rho kinase (ROCK) signaling attenuated these cytokine-induced structural changes. Additionally, RAGE expression was diminished after cytokine stimulation, with release of its soluble isoform via a matrix metalloproteinase (MMP)-9-dependent mechanism. Immunofluorescence microscopy and coimmunoprecipitation revealed association between ERM and RAGE under basal conditions, which was disrupted when challenged with inflammatory cytokines, as ERM in its activated state complexed with membrane-linked CD44. Dual-fluorescence immunohistochemistry of patient idiopathic pulmonary fibrosis (IPF) tissues highlighted marked diminution of RAGE in fibrotic samples, together with enhanced levels of CD44 and double-positive cells for CD44 and phospho (p)ERM. These data suggest that dysregulation of the ERM-RAGE complex might be an important step in rearrangement of the actin cytoskeleton during proinflammatory cytokine-induced EMT of human alveolar epithelial cells.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Mesenchymal Stem Cells Trigger Epithelial to Mesenchymal Transition in the HT-29 Colorectal Cancer Cell Line

Background and Objective: Mesenchymal stem cells (MSCs) promote metastasis in colorectal cancer; however, the mechanism underlying this process is not fully understood. Epithelial to mesenchymal transition (EMT) is a key step in tumor acquisition of metastatic phenotype. We aimed to investigate the effect of MSCs on the expression of EMT markers, as well as cancer stem cell markers in HT-29 col...

متن کامل

Pathogenic interactions between Helicobacter pylori adhesion protein HopQ and human cell surface adhesion molecules CEACAMs in gastric epithelial cells

Objective(s): The present paper aims to review the studies describing the interactions between HopQ and CEACAMs along with possible mechanisms responsible for pathogenicity of Helicobacter pylori.Materials and Methods: The literature was searched on “PubMed” using different key words including Helicobacter pylori, CEACAM and gastric.<br ...

متن کامل

Epithelial to mesenchymal transition concept in Cancer: Review article

Owing to this fact that most of the mortalities in cancers are as a result of metastasis, study on the involved pathways in metastasis including Epithelial to mesenchymal transition (EMT) would be so critical and important. Up to date, several extensive studies have been carried out to determine the correlation between EMT and cancer and their results have shown that the EMT plays pivotal role ...

متن کامل

Crosstalk between Tumor Cells and Immune System Leads to Epithelial-Mesenchymal Transition Induction and Breast Cancer Progression

Herein, we review the current findings of how a variety of accessory cells could participate in shaping the tumor microenvironment and supporting the mechanisms by which cancer cells undertake the epithelial-mesenchymal transition (EMT). EMT, a complex of phenotypic changes, promotes cancer cell invasion and creates resistance to chemotherapies. Among the accessory cells present in the EMT, imm...

متن کامل

Analysis of epithelial mesenchymal transition markers in breast cancer cells in response to stromal cell-derived factor 1

Introduction: Metastasis is the main cause of cancer death; however, the underlying mechanisms of metastasis are largely unknown. The chemokine of stromal cell-derived factor 1 (SDF1) and the process of epithelial mesenchymal transition (EMT), both have been declared as important factors to promote cancer metastasis; however, Conspicuously, the relation between them has not been recognized well...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • American journal of physiology. Lung cellular and molecular physiology

دوره 300 4  شماره 

صفحات  -

تاریخ انتشار 2011