Mice overexpressing latent matrix metalloproteinase-2 develop lung emphysema after short-term exposure to cigarette smoke extract

Onishi, Masahiro; Kobayashi, Tetsu; D’Alessandro-Gabazza, Corina N.; Fujimoto, Hajime; Chelakkot-Govindalayathil, Ayshwarya-Lakshmi; Takahashi, Yūzō; Yasuma, Taro; Nishihama, Kota; Toda, Masaaki; Takei, Yoshiyuki; Taguchi, Osamu; Gabazza, Esteban C.

doi:10.1016/j.bbrc.2018.02.081

Cited by 9 publications

(8 citation statements)

References 31 publications

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“…Aberrant repair alters the physical properties of the lung and limits airflow and, therefore, therapeutics specifically targeting repair could restore lost lung function. Much emphasis has been placed on targeting MMPs and other proteins that regulate the breakdown of ECM to prevent the production of inflammatory products [70]. Another strategy, however, would be to prevent the excessive production of high-molecular weight matrix in the first place.…”

Section: Resultsmentioning

confidence: 99%

The consequence of matrix dysfunction on lung immunity and the microbiome in COPD

et al. 2018

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The pulmonary extracellular matrix (ECM) is a complex network of proteins which primarily defines tissue architecture and regulates various biochemical and biophysical processes. It is a dynamic system comprising two main structures (the interstitial matrix and the basement membrane) which undergo continuous, yet highly regulated, remodelling. This remodelling process is essential for tissue homeostasis and uncontrolled regulation can lead to pathological states including chronic obstructive pulmonary disease (COPD). Altered expression of ECM proteins, as observed in COPD, can contribute to the degradation of alveolar walls and thickening of the small airways which can cause limitations in airflow. Modifications in ECM composition can also impact immune cell migration and retention in the lung with migrating cells becoming entrapped in the diseased airspaces. Furthermore, ECM changes affect the lung microbiome, aggravating and advancing disease progression. A dysbiosis in bacterial diversity can lead to infection, inducing epithelial injury and pro-inflammatory reactions. Here we review the changes noted in the different ECM components in COPD and discuss how an imbalance in microbial commensalism can impact disease development.

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Section: Resultsmentioning

confidence: 99%

The consequence of matrix dysfunction on lung immunity and the microbiome in COPD

et al. 2018

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“…The characterization of human proMMP-2 transgenic (TG) mice in a C57BL/6 background has been previously reported [ 57 , 93 ]. Briefly, the full length of the human proMMP-2 cDNA was prepared and inserted into a vector under the CAG (cytomegalovirus enhancer, first exon and first intron of chicken β -actin gene, splice acceptor of rabbit β-globin gene) promoter, and then microinjected into fertilized eggs from C57BL/6J mice.…”

Section: Methodsmentioning

confidence: 99%

Amelioration of Pulmonary Fibrosis by Matrix Metalloproteinase-2 Overexpression

Inoue

Yasuma

D’Alessandro

et al. 2023

IJMS

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Idiopathic pulmonary fibrosis is a progressive and fatal disease with a poor prognosis. Matrix metalloproteinase-2 is involved in the pathogenesis of organ fibrosis. The role of matrix metalloproteinase-2 in lung fibrosis is unclear. This study evaluated whether overexpression of matrix metalloproteinase-2 affects the development of pulmonary fibrosis. Lung fibrosis was induced by bleomycin in wild-type mice and transgenic mice overexpressing human matrix metalloproteinase-2. Mice expressing human matrix metalloproteinase-2 showed significantly decreased infiltration of inflammatory cells and inflammatory and fibrotic cytokines in the lungs compared to wild-type mice after induction of lung injury and fibrosis with bleomycin. The computed tomography score, Ashcroft score of fibrosis, and lung collagen deposition were significantly reduced in human matrix metalloproteinase transgenic mice compared to wild-type mice. The expression of anti-apoptotic genes was significantly increased, while caspase-3 activity was significantly reduced in the lungs of matrix metalloproteinase-2 transgenic mice compared to wild-type mice. Active matrix metalloproteinase-2 significantly decreased bleomycin-induced apoptosis in alveolar epithelial cells. Matrix metalloproteinase-2 appears to protect against pulmonary fibrosis by inhibiting apoptosis of lung epithelial cells.

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“…In general, TEL contains a large number of macromolecules (e.g., protein, pectin, starch), which are the precursors of harmful substances released by cigarette burning, resulting in increasing irritative smell and mixed gases with an adverse effect (Y. Liu et al, 2018;Onishi et al, 2018). Therefore, the removal of macromolecules from TEL is important to improve the quality of RTS and to reduce the release of harmful components.…”

Section: Introductionmentioning

confidence: 99%

Identification of the coupled fouling mechanism involved in microfiltration of tobacco extracts liquid by multistage Hermia model

Gao

Dong

et al. 2022

J Food Process Engineering

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Microfiltration (MF) is a promising technique widely applied in the separation of solidliquid mixtures. However, the potential application of MF was not explored much in the purification of tobacco extracts liquid. To be efficient, it necessitates having an assessment of the fouling mechanisms involved in MF processing. In this work, a thorough design of experiments was carried out to investigate various operating conditions, while specifying their effects on permeate flux were studied. Both single-stage and multistage Hermia models were used to elucidate the fouling mechanisms. The results of the single-stage Hermia model showed that cake layer formation was the dominant model, yet with fitting accuracy lower than 0.9; the type of fouling mechanism does relate to the operating conditions. Subsequently, the multistage Hermia model was used for determining the fouling mechanism during different time stages. It was found that the determinant coefficients R 2 were significantly increased and multiple fouling mechanisms could be coupled or occurred simultaneously. A ternary plot was established to visualize the contribution of each model and to bridge the relationship between the fouling mechanism and the operating conditions. Therefore, the proposed method is a valid, convenient tool when selecting optimal operating conditions with the lowest irreversible fouling. The flux recovery of fouled membranes exceeded 95% after successive cleaning with deionized water, a 1 wt% NaOH + 0.5 wt% SDS mixed solution, and a 0.5% (vol/vol) HNO 3 solution. Practical ApplicationsCeramic microfiltration membrane could separate tiny particles and macromolecules from tobacco extracts liquid (TEL) while it can keep most of active ingredients. The present study aims to have a better understanding of the complex membrane fouling mechanism in the MF processing of TEL. The fouling mechanism involved in the MF of TEL was firstly reported and a new method to bridge operating conditions and the fouling mechanism was proposed. It demonstrated that it is feasible to reduce irreversible membrane fouling by changing operating conditions during the initial stage of the MF processing. Identification of fouling mechanisms in the present study could be used to postpone fouling of the membranes by optimizing the operating parameters, and reduce irreversible membrane fouling.

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Mice overexpressing latent matrix metalloproteinase-2 develop lung emphysema after short-term exposure to cigarette smoke extract

Cited by 9 publications

References 31 publications

The consequence of matrix dysfunction on lung immunity and the microbiome in COPD

The consequence of matrix dysfunction on lung immunity and the microbiome in COPD

Amelioration of Pulmonary Fibrosis by Matrix Metalloproteinase-2 Overexpression

Identification of the coupled fouling mechanism involved in microfiltration of tobacco extracts liquid by multistage Hermia model

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