YKL-40 mediates airway remodeling in asthma via activating FAK and MAPK signaling pathway

Yu Sun; Zhaoquan Shi; Bing Liu; Xian'Gui Li; Ge Li; Feng Yang; Hao Tang

doi:10.1080/15384101.2020.1750811

YKL-40 mediates airway remodeling in asthma via activating FAK and MAPK signaling pathway

Cell Cycle. 2020 Jun;19(11):1378-1390. doi: 10.1080/15384101.2020.1750811. Epub 2020 Apr 14.

Authors

Yu Sun¹, Zhaoquan Shi², Bing Liu³, Xian'Gui Li⁴, Ge Li², Feng Yang⁴, Hao Tang²

Affiliations

¹ Insititute of Burn Surgery, Changhai Hospital, Second Military Medical University , Shanghai, China.
² Department of Respiratory and Critical Care Medicine, Changzheng Hospital, Second Military Medical University , Shanghai, China.
³ Department of Respiratory Medicine, Shanghai Liqun Hospital , Shanghai, China.
⁴ Department of Inorganic Chemistry, School of Pharmacy, Second Military Medical University , Shanghai, China.

Abstract

YKL-40 is a chitinase-like protein which was significantly elevated in asthma patients and related closely to asthma severity and airway remodeling. Airway remodeling in asthma involves complicated physical and pathological processes, including increased airway smooth muscle mass due to proliferation, migration of airway smooth muscle cells, epithelial-mesenchymal transition (EMT) and sub-epithelial fibrosis. However, the precise effect and underlying mechanism of YKL-40 in this pathological alteration remained unelucidated. In this study, we demonstrated that YKL-40 could promote asthma airway remodeling by increasing airway smooth muscle mass, inducing EMT and sub-epithelial fibrosis. Furthermore, we identified that FAK and MAPK signaling pathways are activated in the process. Inhibiting FAK or MAPK pathway could significantly ameliorate airway remodeling induced by excessive secretion of YKL-40 in vitro. and in vivo. In conclusion, this study shed light upon the effects of YKL-40 in asthma airway remodeling and provided potential novel targets in asthma patients with high YKL-40 level.

Keywords: FAK and MAPK; YKL-40; airway remodeling; asthma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Airway Remodeling* / drug effects
Animals
Asthma / pathology
Asthma / physiopathology*
Cell Movement / drug effects
Cell Proliferation / drug effects
Chitinase-3-Like Protein 1 / metabolism*
Cyclin D1 / metabolism
Cyclin-Dependent Kinases / metabolism
Disease Models, Animal
Epithelial Cells / drug effects
Epithelial Cells / metabolism
Epithelial-Mesenchymal Transition / drug effects
Fibrosis
Focal Adhesion Protein-Tyrosine Kinases / metabolism*
Humans
MAP Kinase Signaling System* / drug effects
Mice, Inbred C57BL
Myocytes, Smooth Muscle / drug effects
Myocytes, Smooth Muscle / metabolism
Protein Kinase Inhibitors / pharmacology
Proto-Oncogene Proteins c-akt / metabolism
src-Family Kinases / metabolism

Substances

Chitinase-3-Like Protein 1
Protein Kinase Inhibitors
Cyclin D1
Focal Adhesion Protein-Tyrosine Kinases
src-Family Kinases
Proto-Oncogene Proteins c-akt
Cyclin-Dependent Kinases

Grants and funding

This research was supported by General Program of National Nature Science Foundation of China [Grant No. 81370137 and No. 81670015], Shanghai Pujiang Program [16PJD006] as well as General Program of Shanghai health and family planning commission [201440503].