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Protectin DX promotes epithelial injury repair and inhibits fibroproliferation partly via ALX/PI3K signalling pathway
- Source :
- Journal of Cellular and Molecular Medicine
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Acute respiratory distress syndrome/acute lung injury (ARDS/ALI) is histologically characterized by extensive alveolar barrier disruption and excessive fibroproliferation responses. Protectin DX (PDX) displays anti‐inflammatory and potent inflammation pro‐resolving actions. We sought to investigate whether PDX attenuates LPS (lipopolysaccharide)‐induced lung injury via modulating epithelial cell injury repair, apoptosis and fibroblasts activation. In vivo, PDX was administered intraperitoneally (IP) with 200 ng/per mouse after intratracheal injection of LPS, which remarkedly stimulated proliferation of type II alveolar epithelial cells (AT II cells), reduced the apoptosis of AT II cells, which attenuated lung injury induced by LPS. Moreover, primary type II alveolar cells were isolated and cultured to assess the effects of PDX on wound repair, apoptosis, proliferation and transdifferentiation in vitro. We also investigated the effects of PDX on primary rat lung fibroblast proliferation and myofibroblast differentiation. Our result suggests PDX promotes primary AT II cells wound closure by inducing the proliferation of AT II cells and reducing the apoptosis of AT II cells induced by LPS, and promotes AT II cells transdifferentiation. Furthermore, PDX inhibits transforming growth factor‐β1 (TGF‐β1) induced fibroproliferation, fibroblast collagen production and myofibroblast transformation. Furthermore, the effects of PDX on epithelial wound healing and proliferation, fibroblast proliferation and activation partly via the ALX/ PI3K signalling pathway. These data present identify a new mechanism of PDX which targets the airway epithelial cell and fibroproliferation are potential for treatment of ARDS/ALI.
- Subjects :
- Lipopolysaccharides
0301 basic medicine
endocrine system
Docosahexaenoic Acids
transdifferentiation
Acute Lung Injury
wound healing
Inflammation
Lung injury
type II alveolar cells
Alveolar cells
Mice
Phosphatidylinositol 3-Kinases
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Anaplastic Lymphoma Kinase
fibroblast proliferation
Fibroblast
PI3K/AKT/mTOR pathway
Chemistry
Angiotensin II
Transdifferentiation
apoptosis
Original Articles
Cell Biology
acute respiratory distress syndrome
Rats
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Alveolar Epithelial Cells
030220 oncology & carcinogenesis
Cancer research
Cytokines
Molecular Medicine
Original Article
Inflammation Mediators
medicine.symptom
Wound healing
Myofibroblast
Subjects
Details
- ISSN :
- 15824934 and 15821838
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular and Molecular Medicine
- Accession number :
- edsair.doi.dedup.....70e4099d50d42e9f7ddfdb1ff710778e