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Increased levels of FOXM1 transcription factor in bronchioalveolar stem cells promote epithelial cell repopulation in injured mouse airway
Author(s) -
Wang IChing,
Chiu YiShiuan,
Chen WeiHsin,
Li ChienCheng,
Lee YunChing
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.817.9
Subject(s) - foxm1 , respiratory epithelium , stem cell , lung , epithelium , pathology , biology , microbiology and biotechnology , andrology , cancer research , immunology , cell , medicine , cell cycle , genetics
Bronchioalveolar stem cells (BASCs) have been shown to maintain the bronchiolar and alveolar epithelial cell renewal upon lung injury. Previously we have shown Foxm1 transcription factors plays essential roles in cellular proliferation, migration, differentiation and tumorigenesis. Conditional deletion of Foxm1 from mouse respiratory epithelium during initial stages of lung development inhibited lung maturation and caused respiratory failure after birth, while deletion of Foxm1 from adult lung airway epithelium reduced club cell proliferation after naphthalene‐induced lung injury. Here, we show that premature expression of transgenic FOXM1accelerated airway epithelial cell proliferation after naphthalene induced lung injury in CCSP‐rtTA/tetO‐FOXM1 mouse (C/FOXM1), which is associated with increased numbers of CC10 and Ki‐67 positive cells in terminal bronchiolar epithelium and bronchioalveolar duct junction (BADJ), the stem cell niche. Lineage tracing experiment showed that FOXM1 promotes proliferation of LacZ or Brainbow labelled naphthalene‐resistant CCSP expressing cells that differentiated into bronchiolar epithelium in healing processes. Co‐immunofluorescent staining showed an increased number of proSPC pos CCSP pos BASCs were found in in BADJ of C/FOXM1 lungs, which consistent to result that an increased number of CD45 neg CD31 neg Sca‐1 hi EpCAM hi bronchiolar stem cells in C/FoxM1 lungs by FASC analysis. Our results indicated that increased expression of FOXM1 contributes to the increases proliferation of lung stem/progenitor cells, and facilitates bronchiolar epithelium repair from acute lung injury. Support or Funding Information National Health Research Institute, Taiwan (NHRI‐EX106‐10309BC); Ministry of Science and Technology, Taiwan (MOST 105‐2628‐B‐007‐003‐MY3); and National Tsing Hua University, Taiwan (106J00X9V8) to I‐C.W. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .