title: The chitinase-like protein YKL-40 increases mucin5AC production in human bronchial epithelial cells.
abstract: Mucus overproduction is an important feature in patients with chronic inflammatory airway diseases. However, the regulatory mechanisms that mediate excessive mucin production remain elusive. Recently, the level of YKL-40, a chitinase-like protein, has been found to be significantly increased in chronic inflammatory airway diseases and has been shown to be associated with the severity of these diseases. In this study, we sought to explore the effect of YKL-40 on mucin5AC (MUC5AC) production in chronic inflammatory airway diseases and the potential signaling pathways involved in this process. We found that elevated YKL-40 levels increased the mRNA and protein expression of MUC5AC in a dose- and time-dependent manner, in association with the phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear factor κB (NF-κB), reflecting their activation. These responses were significantly suppressed by the knockdown of protease-activating receptor 2 (PAR2) with specific small interfering RNA or the inhibitors of ERK and NF-κB. YKL-40-induced MUC5AC overproduction was also effectively attenuated by the inhibitor of focal adhesion kinase (FAK). Taken together, these results imply that YKL-40 can stimulate excessive MUC5AC production through PAR2- and FAK-mediated mechanisms.
authors.affiliation: Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, No. 74, Linjiang Road, Yuzhong District, Chongqing 400010, China.
authors.forename: Chunyi
authors.initials: C
authors.lastname: Liu
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Zhou
authors.forename: Victor P
authors.initials: VP
authors.lastname: Kolosov
authors.forename: Juliy M
authors.initials: JM
authors.lastname: Perelman
mesh_terms: D054392:Adipokines / Q000494:pharmacology* / Q000633:toxicity; D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000071451:Chitinase-3-Like Protein 1; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D037102:Lectins / Q000494:pharmacology* / Q000633:toxicity; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; D055271:Mucin 5AC
keywords: Extracellular signal-regulated kinase; Focal adhesion kinase; Mucin5AC; Nuclear factor κB; Protease-activating receptor 2; YKL-40