Hepatocyte growth factor secreted by bone marrow stem cell reduce ER stress and improves repair in alveolar epithelial II cells
Authors
Izabela Nita, Katrin Hostettler, Luca Tamo, Michaela Medová, Giuseppe Bombaci, Jun Zhong, Ramanjaneyulu Allam, Yitzhak Zimmer, Michael Roth, Thomas Geiser & Amiq Gazdhar
Institution
University Hospital Bern,
Country
Switzerland
Year
2017
Journal
Nature - Scientific Reports
Abstract
Idiopathic Pulmonary Fibrosis (IPF) is a progressive, irreversible lung disease with complex
pathophysiology. Evidence of endoplasmic reticulum (ER) stress has been reported in alveolar
epithelial cells (AEC) in IPF patients. Secreted mediators from bone marrow stem cells (BMSC-cm) have
regenerative properties. In this study we investigate the beneficial effects of BMSC-cm on ER stress
response in primary AEC and ER stressed A549 cells. We hypothesize that BMSC-cm reduces ER stress.
Primary AEC isolated from IPF patients were treated with BMSC-cm. To induce ER stress A549 cells were
incubated with Tunicamycin or Thapsigargin and treated with BMSC-cm, or control media. Primary
IPF-AEC had high Grp78 and CHOP gene expression, which was lowered after BMSC-cm treatment.
Similar results were observed in ER stressed A549 cells. Alveolar epithelial repair increased in presence
of BMSC-cm in ER stressed A549 cells. Hepatocyte growth factor (HGF) was detected in biologically
relevant levels in BMSC-cm. Neutralization of HGF in BMSC-cm attenuated the beneficial effects of
BMSC-cm including synthesis of surfactant protein C (SP-C) in primary AEC, indicating a crucial role
of HGF in ER homeostasis and alveolar epithelial repair. Our data suggest that BMSC-cm may be a
potential therapeutic option for treating pulmonary fibrosis.