scholarly journals Regulation of the IGF1 signaling pathway is involved in idiopathic pulmonary fibrosis induced by alveolar epithelial cell senescence and core fucosylation

Aging ◽  
2021 ◽  
Author(s):  
Wei Sun ◽  
Xiaoyan Jing ◽  
Xiaoyu Yang ◽  
Hui Huang ◽  
Qun Luo ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Alveolar Epithelial Cell ◽  
Cell Senescence ◽  
Alveolar Epithelial ◽  
Core Fucosylation

scholarly journals Grainyhead-like 2 (GRHL2) distribution reveals novel pathophysiological differences between human idiopathic pulmonary fibrosis and mouse models of pulmonary fibrosis

2014 ◽  
Vol 306 (5) ◽  
pp. L405-L419 ◽  
Author(s):  
Saaket Varma ◽  
Poornima Mahavadi ◽  
Satish Sasikumar ◽  
Leah Cushing ◽  
Tessa Hyland ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Mouse Models ◽  
Human Lung ◽  
Alveolar Epithelial Cell ◽  
Lung Epithelium ◽  
Chronic Injury ◽  
Alveolar Epithelial

Chronic injury of alveolar lung epithelium leads to epithelial disintegrity in idiopathic pulmonary fibrosis (IPF). We had reported earlier that Grhl2, a transcriptional factor, maintains alveolar epithelial cell integrity by directly regulating components of adherens and tight junctions and thus hypothesized an important role of GRHL2 in pathogenesis of IPF. Comparison of GRHL2 distribution at different stages of human lung development showed its abundance in developing lung epithelium and in adult lung epithelium. However, GRHL2 is detected in normal human lung mesenchyme only at early fetal stage (week 9). Similar mesenchymal reexpression of GRHL2 was also observed in IPF. Immunofluorescence analysis in serial sections from three IPF patients revealed at least two subsets of alveolar epithelial cells (AEC), based on differential GRHL2 expression and the converse fluorescence intensities for epithelial vs. mesenchymal markers. Grhl2 was not detected in mesenchyme in intraperitoneal bleomycin-induced injury as well as in spontaneously occurring fibrosis in double-mutant HPS1 and HPS2 mice, whereas in contrast in a radiation-induced fibrosis model, with forced Forkhead box M1 (Foxm1) expression, an overlap of Grhl2 with a mesenchymal marker was observed in fibrotic regions. Grhl2's role in alveolar epithelial cell plasticity was confirmed by altered Grhl2 gene expression analysis in IPF and further validated by in vitro manipulation of its expression in alveolar epithelial cell lines. Our findings reveal important pathophysiological differences between human IPF and specific mouse models of fibrosis and support a crucial role of GRHL2 in epithelial activation in lung fibrosis and perhaps also in epithelial plasticity.

Involvement of Alveolar Epithelial Cell Necroptosis in Idiopathic Pulmonary Fibrosis Pathogenesis

2018 ◽  
Vol 59 (2) ◽  
pp. 215-224 ◽  
Author(s):  
Ji-Min Lee ◽  
Masahiro Yoshida ◽  
Mi-So Kim ◽  
June-Hyuk Lee ◽  
Ae-Rin Baek ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial

scholarly journals PTEN loss regulates alveolar epithelial cell senescence in pulmonary fibrosis depending on Akt activation

Aging ◽  
2019 ◽  
Vol 11 (18) ◽  
pp. 7492-7509 ◽  
Author(s):  
Ting Qiu ◽  
Yaqiong Tian ◽  
Yujuan Gao ◽  
Miao Ma ◽  
Hui Li ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Pulmonary Fibrosis ◽  
Alveolar Epithelial Cell ◽  
Cell Senescence ◽  
Pten Loss ◽  
Akt Activation ◽  
Alveolar Epithelial

scholarly journals Fisetin Alleviated Bleomycin-Induced Pulmonary Fibrosis Partly by Rescuing Alveolar Epithelial Cells From Senescence

2020 ◽  
Vol 11 ◽  
Author(s):  
Li Zhang ◽  
Xiang Tong ◽  
Jizhen Huang ◽  
Man Wu ◽  
Shijie Zhang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Alveolar Epithelial Cell ◽  
Cell Senescence ◽  
Alveolar Epithelial Cells ◽  
Inflammatory Factors ◽  
Collagen Deposition ◽  
Alveolar Epithelial ◽  
Compound C

Idiopathic pulmonary fibrosis is an aging-associated disease, satisfactory therapies are not yet available. Accelerated senescence of alveolar epithelial cells plays an important part in Idiopathic pulmonary fibrosis pathogenesis. Fisetin (FIS) is a natural non-toxic flavonoid, which has many pharmacological functions. However, the role of FIS in pulmonary fibrosis has not been established. In this study, we found that FIS treatment apparently alleviated BLM-induced weight loss, inflammatory cells infiltration, inflammatory factors expression, collagen deposition and alveolar epithelial cell senescence, along with AMPK activation and the down regulation of NF-κB and TGF-β/Smad3 in vivo. In vitro, FIS administration significantly inhibited the senescence of alveolar epithelial cells and senescence-associated secretory phenotype, followed by reduced transdifferentiation of fibroblasts to myofibroblasts as well as collagen deposition in fibroblasts, which was blocked by an AMPK inhibitor, Compound C. Together, these results suggest that FIS can alleviate the development of BLM-induced pulmonary fibrosis, which is related to the inhibition of TGF-β/Smad3 signaling and the reduction of alveolar epithelium cell senescence by regulating AMPK/NF-κB signaling pathway. FIS may be a promising candidate for patients with pulmonary fibrosis.

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