Abstract

Trans-differentiation of Alveolar Epithelial Type II Cells to Type I Cells Involves Autocrine Signaling by Transforming Growth Factor β1 through the Smad Pathway

Highlights

  • transforming growth factor ␤1 (TGF ␤1) and Smad4 Were Highly Expressed in Alveolar epithelial cells (AEC) II—To identify cellular localization of transforming growth factor ␤ (TGF ␤)1 and Smad4, double immunolabeling was performed on perfused normal rat lung

  • The results revealed a strong co-localization of both proteins with surfactant protein C (SP-C) in AEC II (Fig. 1)

  • TGF ␤1 has been reported to be expressed in alveolar epithelial cells under pathological conditions

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Summary

Introduction

AEC II cell proliferation and hyperplasia, followed by trans-differentiation into AEC I is a hallmark of alveolar epithelial injury. A member of this family, TGF ␤1, regulates cell proliferation, differentiation, and migration in many cell and tissue systems. TGF ␤ can inhibit the transcription of genes needed for the cell cycle progression This includes c-Myc [15,16,17] and CDK activating phosphatase, cdc25A [18]. Through the addition of TGF ␤1 and its neutralizing antibody, RNA interference (RNAi)-mediated silencing of Smad and by showing differential expression of the components of TGF ␤ pathway and cell cycle proteins during the trans-differentiation process, we have demonstrated a possible mechanism of controlling this process in the alveolar epithelium

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