Intratracheal transplantation of mesenchymal stem cells attenuates hyperoxia-induced lung injury by down-regulating, but not direct inhibiting formyl peptide receptor 1 in the newborn mice

PLoS One. 2018 Oct 24;13(10):e0206311. doi: 10.1371/journal.pone.0206311. eCollection 2018.

Abstract

Formyl peptide receptor 1 (FPR1) has been shown to be a key regulator of inflammation. However, its role in bronchopulmonary dysplasia (BPD) has not been delineated yet. We investigated whether FPR1 plays a pivotal role in regulating lung inflammation and injuries, and whether intratracheally transplanted mesenchymal stem cells (MSCs) attenuate hyperoxic lung inflammation and injuries by down-regulating FPR1. Newborn wild type (WT) or FPR1 knockout (FPR1-/-) C57/BL6 mice were randomly exposed to 80% oxygen or room air for 14 days. At postnatal day (P) 5, 2×10(5) MSCs were intratracheally transplanted. At P14, mice were sacrificed for histopathological and morphometric analyses. Hyperoxia significantly increased lung neutrophils, macrophages, and TUNEL-positive cells, while impairing alveolarization and angiogenesis, along with a significant increase in FPR1 mRNA levels in WT mice. The hyperoxia-induced lung inflammation and lung injuries were significantly attenuated, with the reduced mRNA level of FPR1, in WT mice with MSC transplantation and in FPR1-/- mice, irrespective of MSCs transplantation. However, only MSC transplantation, but not the FPR1 knockout, significantly attenuated the hyperoxia-induced increase in TUNEL-positive cells. Our findings indicate that FPR1 play a critical role in regulating lung inflammation and injuries in BPD, and MSCs attenuate hyperoxic lung inflammation and injuries, but not apoptosis, with down regulating, but not direct inhibiting FPR1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hyperoxia / pathology*
  • Lung / pathology*
  • Lung Injury / prevention & control
  • Mesenchymal Stem Cell Transplantation*
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / metabolism
  • Receptors, Formyl Peptide / genetics*
  • Receptors, Formyl Peptide / metabolism
  • Signal Transduction
  • Trachea / transplantation*

Substances

  • Fpr1 protein, mouse
  • RNA, Messenger
  • Receptors, Formyl Peptide

Grants and funding

This work was supported by grants HI12C1821 and HI14C3484 from the Korean Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Young Eun Kim and Yun Sil Chang are employed by Samsung Advanced Institute for Health Sciences and Technology (SAIHST). Won Soon Park, Ahn So Yoon, Dong Kyung Sung and Yun Sil Chang are employed by Samsung Medical Center. Won Soon Park, DongKyung Sung and Yun Sil Chang are employed by Samsung Biomedical Research Institute. Samsung Biomedical Research Institute, Samsung Advanced Institute for Health Sciences and Technology and Samsung Medical Center provided support in the form of salaries for authors YEK, YSC, WSP, ASY and DKS, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.