Alteration in the Wnt microenvironment directly regulates molecular events leading to pulmonary senescence

Tamas Kovacs, Veronika Csongei, Diana Feller, David Ernszt, Gabor Smuk, Veronika Sarosi, Laszlo Jakab, Krisztian Kvell, Domokos Bartis, Judit E. Pongracz

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20 Citations (Scopus)

Abstract

In the aging lung, the lung capacity decreases even in the absence of diseases. The progenitor cells of the distal lung, the alveolar type II cells (ATII), are essential for the repair of the gas-exchange surface. Surfactant protein production and survival of ATII cells are supported by lipofibroblasts that are peroxisome proliferator-activated receptor gamma (PPARγ)-dependent special cell type of the pulmonary tissue. PPARγ levels are directly regulated by Wnt molecules; therefore, changes in the Wnt microenvironment have close control over maintenance of the distal lung. The pulmonary aging process is associated with airspace enlargement, decrease in the distal epithelial cell compartment and infiltration of inflammatory cells. qRT-PCR analysis of purified epithelial and nonepithelial cells revealed that lipofibroblast differentiation marker parathyroid hormone-related protein receptor (PTHrPR) and PPARγ are reduced and that PPARγ reduction is regulated by Wnt4 via a β-catenin-dependent mechanism. Using a human in vitro 3D lung tissue model, a link was established between increased PPARγ and pro-surfactant protein C (pro-SPC) expression in pulmonary epithelial cells. In the senile lung, both Wnt4 and Wnt5a levels increase and both Wnt-s increase myofibroblast-like differentiation. Alteration of the Wnt microenvironment plays a significant role in pulmonary aging. Diminished lipo- and increased myofibroblast-like differentiation are directly regulated by specific Wnt-s, which process also controls surfactant production and pulmonary repair mechanisms.

Original languageEnglish
Pages (from-to)838-849
Number of pages12
JournalAging cell
Volume13
Issue number5
DOIs
Publication statusPublished - Oct 1 2014

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Keywords

  • Molecular biology of aging
  • Pulmonary senescence
  • Wnt microenvironment

ASJC Scopus subject areas

  • Ageing
  • Cell Biology

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