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자료유형
학술저널
저자정보
Jinli Wang (Jinan Central Hospital Affiliated to Shandong University) Hongyang Zhao (Jinan Central Hospital Affiliated to Shandong University) Fenfen Xu (Jinan Central Hospital Affiliated to Shandong University) Piaopiao Zhang (Graduate School of Taishan Medical University) Yuan Zheng (Jinan Central Hospital Affiliated to Shandong University) Nan Jia (The Second Affiliated Hospital of Xi’an Medical College)
저널정보
한국유전학회 Genes & Genomics Genes & Genomics Vol.41 No.9
발행연도
2019.1
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1,045 - 1,053 (9page)

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Background Cystic pulmonary fibrosis (CF) affects mostly the lung of the newborns. Chronic infection and inflammation become the major causes of morbidity and mortality in CF. However, the underlying molecular mechanisms causing CF still remain unclear. Methods ELISA assay was used to examine the expression of HE4 and pro-inflammatory cytokines in W126VA4 cells supernatant fluid. qRT-PCR was applicable to determine the mRNA level of HE4, α-SMA, collagen 1, MMP2, MMP9 and various interleukins. Immunofluorescent assay was used to test the expression of HE4 in WI-26 VA4 cells. Major elements of MAPK and NF-κB signals pathways were examined by western blot. Results We found higher expression of HE4 in CF patients serum and lung biopsy. Interestingly, HE4 expression was positively correlated with fibrosis markers expression. In addition,HE4 overexpression increased inflammatory cytokines secretion and fibrosis markers expression in WI-26 VA4 cells. And NF-κB pathways were responsible for elevated inflammation. In addition, HE4/MAPK/MMPs signaling cascades destroyed the normal extracellular matrix (ECM) and promoted fibrosis. Conclusions Overall, we first identified that HE4 promoted CF-associated inflammation. Additionally, NF-κB and MAPK signalings were further validated to be responsible for CF-associated inflammation and ECM destruction. Characterization of lumacaftor/ivacaftor in CF-associated inflammation may provide a novel insight into clinical CF treatment.

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