TY - JOUR
AB - Idiopathic pulmonary fibrosis (IPF) is a progressive and devastating interstitial lung disease. The origin of myofibroblasts is still to be elucidated and the existence of epithelial‑mesenchymal transition (EMT) in IPF remains controversial. Hence, it is important to clarify the origin of fibroblasts by improving modeling and labeling methods and analyzing the differentiation pathway of alveolar epithelial cells (AEC) in pulmonary fibrosis with cell tracking technology. In the present study, adult transgenic mice with SPC‑rtTA+/‑/tetO7‑CMV‑Cre+/‑/mTmG+/‑ were induced with doxycycline for 15 days. The gene knockout phenomenon occurred in type II AECs in the lung and the reporter gene cell membrane‑localized enhanced green fluorescence protein (mEGFP) was expressed in the cell membrane. The expression of Cre recombinase and SPC was analyzed using immunohistochemical (IHC) staining to detect the labeling efficiency. A repetitive intraperitoneal bleomycin‑induced pulmonary fibrosis model was established, and the mice were sacrificed on day 28. The co‑localization of mEGFP and mesenchymal markers α‑smooth muscle actin (α‑SMA) and S100 calcium binding protein A4 (S100A4) were detected by multiple IHC staining. The results revealed that Cre was expressed in the airway and AECs in the lung tissue of adult transgenic mice with SPC‑rtTA+/‑/tetO7‑CMV‑Cre+/‑/mTmG+/‑ induced by doxycycline; the labeling efficiency in the peripheral lung tissue was 63.27±7.51%. mEGFP was expressed on the membrane of type II AECs and their differentiated form of type I AECs. Expression of mEGFP was mainly observed in the fibrotic region in bleomycin‑induced pulmonary fibrosis; 1.94±0.08% of α‑SMA‑positive cells were mEGFP‑positive and 9.68±2.06% of S100A4‑positive cells were mEGFP‑positive in bleomycin‑induced pulmonary fibrosis. In conclusion, the present results suggested that while EMT contributes to the pathogenesis of pulmonary fibrosis, it is not the major causative factor of this condition.
AD - Department of Developmental Cell Biology, Key Laboratory of Cell Biology of The Ministry of Public Health, Key Laboratory of Medical Cell Biology of The Ministry of Education, China Medical University, Shenyang, Liaoning 110122, P.R. China
AU - Tan,Wei
AU - Wang,Yaru
AU - Chen,Yuhua
AU - Chen,Cheng
DA - 2021/10/01
DO - 10.3892/etm.2021.10622
IS - 4
JO - Exp Ther Med
KW - bleomycin
epithelial‑mesenchymal transition
idiopathic pulmonary fibrosis
cell tracing
multiple IHC staining
PY - 2021
SN - 1792-0981
1792-1015
SP - 1188
ST - Cell tracing reveals the transdifferentiation fate of mouse lung epithelial cells during pulmonary fibrosis in vivo
T2 - Experimental and Therapeutic Medicine
TI - Cell tracing reveals the transdifferentiation fate of mouse lung epithelial cells during pulmonary fibrosis in vivo
UR - https://doi.org/10.3892/etm.2021.10622
VL - 22
ER -