MMP-10 from M1 macrophages promotes pulmonary vascular remodeling and pulmonary arterial hypertension

Chi, Pei‐Ling; Cheng, Chin-Chang; Hung, Cheng-Chung; Wang, Mei-Tzu; Liu, Hsien-Yueh; Ke, Meng-Wei; Shen, Min-Ci; Lin, Kung‐Hung; Kuo, Shu-Hung; Hsieh, Pin‐Pen; Wann, Shue-Ren; Huang, Wei-Chun

doi:10.7150/ijbs.66472

Cited by 28 publications

(20 citation statements)

References 32 publications

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“…We confirmed that the activation and accumulation of fibroblasts significantly induced the synthesis of type I collagen, which is a key element in pulmonary fibrosis. Another important feature of pulmonary fibrosis is pulmonary remodeling [ 44 ]. We found that IL-1β induced TIMP-1 and MMP-3 expression, indicating the role of IL-1β in pulmonary remodeling.…”

Section: Discussionmentioning

confidence: 99%

Activation of NLRP3 inflammasome in lung epithelial cells triggers radiation-induced lung injury

et al. 2023

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Background Radiation-induced lung injury (RILI) is the most common and serious complication of chest radiotherapy. However, reported radioprotective agents usually lead to radiation resistance in tumor cells. The key to solving this problem is to distinguish between the response of tumor cells and normal lung epithelial cells to radiation damage. Methods RNA-Seq was used to recognize potential target of alleviating the progression of RILI as well as inhibiting tumor growth. The activation of NLRP3 inflammasome in lung epithelial cells was screened by qRT-PCR, western blotting, immunofluorescence, and ELISA. An in vivo model of RILI and in vitro conditioned culture model were constructed to evaluate the effect of NLRP3/interleukin-1β on fibroblasts activation. ROS, ATP, and (NADP)+/NADP(H) level in lung epithelial cells was detected to explore the mechanism of NLRP3 inflammasome activation. The lung macrophages of the mice were deleted to evaluate the role of lung epithelial cells in RILI. Moreover, primary cells were extracted to validate the results obtained from cell lines. Results NLRP3 activation in epithelial cells after radiation depends on glycolysis-related reactive oxygen species accumulation. DPYSL4 is activated and acts as a negative regulator of this process. The NLRP3 inflammasome triggers interleukin-1β secretion, which directly affects fibroblast activation, proliferation, and migration, eventually leading to lung fibrosis. Conclusions Our study suggests that NLRP3 inflammasome activation in lung epithelial cells is essential for radiation-induced lung injury. These data strongly indicate that targeting NLRP3 may be effective in reducing radiation-induced lung injury in clinical settings.

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Section: Discussionmentioning

confidence: 99%

Activation of NLRP3 inflammasome in lung epithelial cells triggers radiation-induced lung injury

et al. 2023

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“…MMP-10 is expressed by macrophages and CD68-positive cells in the lungs and, to a lesser extent, by epithelial cells in response to acute inflammatory conditions [ 56 , 89 ]. Macrophage-derived MMP-10 mitigates the proinflammatory response by controlling macrophage activation through restraint of M1 polarization and promoting the ability of M2 macrophages to control the expression of gelatinolytic MMPs, particularly MMP-13 [ 90 , 91 ].…”

Section: Mmps In Copdmentioning

confidence: 99%

Matrix Metalloproteinases in Chronic Obstructive Pulmonary Disease

Christopoulou

Papakonstantinou

Stolz

2023

IJMS

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Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade proteins of the extracellular matrix and the basement membrane. Thus, these enzymes regulate airway remodeling, which is a major pathological feature of chronic obstructive pulmonary disease (COPD). Furthermore, proteolytic destruction in the lungs may lead to loss of elastin and the development of emphysema, which is associated with poor lung function in COPD patients. In this literature review, we describe and appraise evidence from the recent literature regarding the role of different MMPs in COPD, as well as how their activity is regulated by specific tissue inhibitors. Considering the importance of MMPs in COPD pathogenesis, we also discuss MMPs as potential targets for therapeutic intervention in COPD and present evidence from recent clinical trials in this regard.

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“…Inflammation-induced overproduction of ECM components in cardiovascular diseases is rivaled by elevated proteolytic ECM degradation via a parallel increase in MMPs ( 46 ). In PH, activated macrophages and myofibroblasts in the adventitia secrete MMPs, specifically MMP-2 ( 154 , 162 ), MMP-9 ( 6 , 162 ), MMP-10 ( 47 ), and MMP-19 ( 6 , 154 ), while tissue inhibitors of metalloproteinases (TIMPs) appear downregulated ( 46 , 162 ) ( Table 2 ; Figure 2 ). MMP-2 ( 50 ) and MMP-9 ( 49 ) degrade elastin, thereby decreasing vessel compliance, resulting in arterial stiffening ( 49 – 52 ).…”

Section: Inflammation-induced Arterial Wall Thickening and Ecm Remode...mentioning

confidence: 99%

“…Additionally, increased expression of other ECM proteins such as elastin and fibronectin, or the matricellular ECM protein tenascin-C by dedifferentiated adventitial fibroblasts has been reported in PAH patients ( 46 ). Increased production and deposition of ECM constituents in PAs is considered to occur as an adaptive response to increased digestion of medial and basement membrane (BM) ECM by matrix metalloproteinases (MMPs), which have been found to be increased in PAH ( 47 ) and IPAH patients ( 45 ). The elevated expression of collagens by endothelial cells (ECs), smooth muscle cells (SMCs), and adventitial fibroblasts is associated with increased collagen-cross-linking by lysyl oxidases (LOXs) ( 48 ).…”

Section: Introductionmentioning

confidence: 99%

Pulmonary hypertension: Linking inflammation and pulmonary arterial stiffening

Liu

Veetil

et al. 2022

Front. Immunol.

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Pulmonary hypertension (PH) is a progressive disease that arises from multiple etiologies and ultimately leads to right heart failure as the predominant cause of morbidity and mortality. In patients, distinct inflammatory responses are a prominent feature in different types of PH, and various immunomodulatory interventions have been shown to modulate disease development and progression in animal models. Specifically, PH-associated inflammation comprises infiltration of both innate and adaptive immune cells into the vascular wall of the pulmonary vasculature—specifically in pulmonary vascular lesions—as well as increased levels of cytokines and chemokines in circulating blood and in the perivascular tissue of pulmonary arteries (PAs). Previous studies suggest that altered hemodynamic forces cause lung endothelial dysfunction and, in turn, adherence of immune cells and release of inflammatory mediators, while the resulting perivascular inflammation, in turn, promotes vascular remodeling and the progression of PH. As such, a vicious cycle of endothelial activation, inflammation, and vascular remodeling may develop and drive the disease process. PA stiffening constitutes an emerging research area in PH, with relevance in PH diagnostics, prognostics, and as a therapeutic target. With respect to its prognostic value, PA stiffness rivals the well-established measurement of pulmonary vascular resistance as a predictor of disease outcome. Vascular remodeling of the arterial extracellular matrix (ECM) as well as vascular calcification, smooth muscle cell stiffening, vascular wall thickening, and tissue fibrosis contribute to PA stiffening. While associations between inflammation and vascular stiffening are well-established in systemic vascular diseases such as atherosclerosis or the vascular manifestations of systemic sclerosis, a similar connection between inflammatory processes and PA stiffening has so far not been addressed in the context of PH. In this review, we discuss potential links between inflammation and PA stiffening with a specific focus on vascular calcification and ECM remodeling in PH.

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MMP-10 from M1 macrophages promotes pulmonary vascular remodeling and pulmonary arterial hypertension

Cited by 28 publications

References 32 publications

Activation of NLRP3 inflammasome in lung epithelial cells triggers radiation-induced lung injury

Activation of NLRP3 inflammasome in lung epithelial cells triggers radiation-induced lung injury

Matrix Metalloproteinases in Chronic Obstructive Pulmonary Disease

Pulmonary hypertension: Linking inflammation and pulmonary arterial stiffening

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