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Comparative Study
. 2022 Jan 18;23(1):11.
doi: 10.1186/s12931-021-01920-8.

"VSports手机版" MUC5B regulates goblet cell differentiation and reduces inflammation in a murine COPD model

Xuan Huang  1 , Weijie Guan  1 , Bin Xiang  1 , Wei Wang  1 , Yanqing Xie  1 , Jinping Zheng  2
Affiliations
Comparative Study

MUC5B regulates goblet cell differentiation and reduces inflammation in a murine COPD model (VSports)

Xuan Huang et al. Respir Res. .

Abstract

Background: Airway mucus hypersecretion is one of the important pathological features of chronic obstructive pulmonary disease (COPD). MUC5B is the main mucin expressed in the airways of COPD patients and has been indicated to play an important role in airway defense VSports手机版. However, the specific biological function of MUC5B in COPD and the possible mechanism are not clear. .

Methods: We established a COPD model with 24-week-old MUC5B-/- mice exposed to cigarette smoke and tested our hypothesis through lung function tests, HE and PAS staining, immunohistochemistry (IHC), western blot, q-PCR and ELISA V体育安卓版. .

Results: Compared with MUC5B+/+ mice, MUC5B-/- mice had worse general condition and lung function, increased inflammatory infiltration, reduced goblet cell differentiation as indicated by decreased PAS staining (PAS grade: 1. 8 ± 0. 24 vs. 0. 6 ± 0. 16), reduced MUC5AC expression (ELISA: 0. 30 ± 0. 01 vs. 0. 17 ± 0. 01 mg/ml, q-PCR: 9. 4 ± 1. 7 vs. 4. 1 ± 0. 1 fold, IHC score: 3 V体育ios版. 1 ± 0. 9 vs. 1. 6 ± 0. 7), increased macrophage secretion of inflammatory factors (TNF-α and IL-6) and expression of downstream pathway factors (ERK1/2 and NF-κB), decreased expression of SPDEF and STAT6, and increased expression of FOXA2. .

Conclusion: The protective effect of MUC5B in the development of COPD was mediated by the promotion of goblet cell differentiation and the inhibition of inflammation. The role of MUC5B in regulating inflammation was related to macrophage function, and goblet cell differentiation was promoted by the induced expression of STAT6 and SPDEF. This study describes a mechanism of mucus hypersecretion and identifies MUC5B as a new target for the treatment of mucus hypersecretion VSports最新版本. .

Keywords: COPD; Goblet cell differentiation; Inflammation; MUC5B; SPDEF V体育平台登录. .

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures (VSports app下载)

Fig. 1
Fig. 1
MUC5B−/− mice have decreased goblet cell differentiation. MUC5B+/+ mice (n = 15 per group) and MUC5B−/− mice (n = 10 per group). a PAS staining. b MUC5AC IHC. c PAS grade. d MUC5AC IHC score. e ELISA of MUC5AC in BAL fluid. f RT-qPCR of MUC5AC in lung tissue. g ELISA of MUC5B in BAL fluid. h RT-qPCR of MUC5B in lung tissue. “*” indicates a significant difference; ***P < 0.001, **P < 0.01 compared with smoke-exposed MUC5B+/+ mice
Fig. 2
Fig. 2
MUC5B−/− mice had more severe pulmonary inflammation. a HE staining in the control group. b–d HE staining in the smoke-exposed group: b emphysema; c neutrophil infiltration; d macrophage infiltration; e total leukocytes, f neutrophils and g macrophages in bronchoalveolar lavage fluid (BALF). h inflammation score. “*” indicates a significant difference; ***P < 0.001 compared with smoke-exposed MUC5B+/+ mice
Fig. 3
Fig. 3
MUC5B−/− mice have decreased SPDEF expression. MUC5B+/+ mice (n = 15 per group) and MUC5B−/− mice (n = 10 per group). a SPDEF immunohistochemical staining and IHC score. b STAT6 immunohistochemical staining and positive cell percentage. c FOXA2 immunohistochemical staining and positive cell percentage. d SPDEF western blot and grayscale analysis. e STAT6 western blot and grayscale analysis. f FOXA2 western blot and grayscale analysis. “-” indicates a significant difference between two groups. “*” indicates a significant difference; ***P < 0.001, **P < 0.01, *P < 0.05 compared to smoke-exposed MUC5B+/+ mice
Fig. 4
Fig. 4
MUC5B−/− mice have increased expression of macrophage-related inflammatory factors. MUC5B+/+ mice (n = 15 per group) and MUC5B−/− mice (n = 10 per group). a BAL fluid IL-6 ELISA. b BAL fluid TNF-α ELISA. c ERK1/2 western blot and grayscale analysis. d NF-κB western blot and grayscale analysis. “*” indicates a significant difference; ***P < 0.001, **P < 0.01 compared to smoke-exposed MUC5B+/+ mice
Fig. 5
Fig. 5
General conditions and lung function: MUC5B+/+ mice (n = 15 per group) and MUC5B−/− mice (n = 10 per group). All tests were conducted after the end of model establishment. a Survival curves. b Weight change. c Functional residual capacity (FRC). d Forced expiratory volume in the first 100 ms (FEV100). e Airway resistance (RI). f Dynamic lung compliance (Cdyn). “*” indicates a significant difference; ***P < 0.001, **P < 0.01, *P < 0.05 compared to the smoke-exposed group of MUC5B+/+ mice
Fig. 6
Fig. 6
The cascade amplification process of goblet cell differentiation in the lung. Arrows indicate promotion, and line-capped lines indicate inhibition
See this image and copyright information in PMC

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