Osteopontin N-Terminal Function in an Abdominal Aortic Aneurysm From Apolipoprotein E-Deficient Mice
The cleavage of osteopontin (OPN) by thrombin results in an N-terminal fragment (OPN-N), which exposes a cryptic integrin-binding motif that promotes the adherence of cells, and plays a proinflammatory role. However, the effect of OPN-N on abdominal aortic aneurysm (AAA) remains unknown. The aim of...
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doaj-c6fe3482c3114ff69a8a8073bde19c4f2021-08-12T08:33:56ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-08-01910.3389/fcell.2021.681790681790Osteopontin N-Terminal Function in an Abdominal Aortic Aneurysm From Apolipoprotein E-Deficient MiceHongyang Liu0Ying Zhang1Wei Song2Yancui Sun3Yinong Jiang4Department of Heart Intensive Care Unit, The First Affiliated Hospital of Dalian Medical University, Dalian, ChinaDepartment of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, ChinaDepartment of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, ChinaDepartment of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, ChinaDepartment of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, ChinaThe cleavage of osteopontin (OPN) by thrombin results in an N-terminal fragment (OPN-N), which exposes a cryptic integrin-binding motif that promotes the adherence of cells, and plays a proinflammatory role. However, the effect of OPN-N on abdominal aortic aneurysm (AAA) remains unknown. The aim of this study was to investigate the expression of OPN-N in aortic tissue samples obtained from patients, who underwent acute aortic dissection (AD), and normal aorta, effect of OPN-N on angiotensin (Ang) II-induced AAA in mice, and relationship between OPN-N and pyroptosis-related inflammatory factors in vitro. Hematoxylin and eosin staining was conducted to detect histological changes. Next, we detected the expression of the OPN-N protein. Additionally, ApoE−/− mice were divided into four groups: control, control + M5Ab (to block the OPN-N function in mice), Ang II, and Ang II + M5Ab. All mice were euthanized after a 28-day infusion and whole aortas, including thoracic and abdominal aortas, were collected for morphological and histological analysis of the AAA. The OPN-N protein expression was higher in patients with AD than in normal individuals, while histological changes in the aortas of Ang II mice were suppressed in Ang II + M5Ab mice. The expression of OPN-N, NOD-, LRR-, and pyrin domain-containing protein 3, pro-Caspase-1, ASC, Gasdermin-d, interleukin (IL)-18, IL-1β, matrix metalloproteinase (MMP) 2, and MMP9 was lower in the Ang II + M5Ab group than in the Ang II group. The gene expression of monocyte chemoattractant protein-1, IL-6, and tumor necrosis factor-α was suppressed in the aortic tissues of the Ang II + M5Ab group compared with the Ang II group. Moreover, the expression of α-smooth muscle actin was lower in the Ang II group than in the Ang II + M5Ab group. In vitro results showed that the increase in the expression of pyroptosis-related inflammatory factors induced by OPN was mediated through the nuclear factor (NF)-κB pathway. In conclusion, OPN-N promotes AAA by increasing the expression of pyroptosis-related inflammatory factors through the NF-κB pathway, inflammation, and extracellular matrix degradation. These results highlight the potential of OPN-N as a new therapeutic target to prevent AAA expansion.https://www.frontiersin.org/articles/10.3389/fcell.2021.681790/fullosteopontin N-terminalabdominal aortic aneurysmpyroptosisApoE-/- miceinflammation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hongyang Liu Ying Zhang Wei Song Yancui Sun Yinong Jiang |
spellingShingle |
Hongyang Liu Ying Zhang Wei Song Yancui Sun Yinong Jiang Osteopontin N-Terminal Function in an Abdominal Aortic Aneurysm From Apolipoprotein E-Deficient Mice Frontiers in Cell and Developmental Biology osteopontin N-terminal abdominal aortic aneurysm pyroptosis ApoE-/- mice inflammation |
author_facet |
Hongyang Liu Ying Zhang Wei Song Yancui Sun Yinong Jiang |
author_sort |
Hongyang Liu |
title |
Osteopontin N-Terminal Function in an Abdominal Aortic Aneurysm From Apolipoprotein E-Deficient Mice |
title_short |
Osteopontin N-Terminal Function in an Abdominal Aortic Aneurysm From Apolipoprotein E-Deficient Mice |
title_full |
Osteopontin N-Terminal Function in an Abdominal Aortic Aneurysm From Apolipoprotein E-Deficient Mice |
title_fullStr |
Osteopontin N-Terminal Function in an Abdominal Aortic Aneurysm From Apolipoprotein E-Deficient Mice |
title_full_unstemmed |
Osteopontin N-Terminal Function in an Abdominal Aortic Aneurysm From Apolipoprotein E-Deficient Mice |
title_sort |
osteopontin n-terminal function in an abdominal aortic aneurysm from apolipoprotein e-deficient mice |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-08-01 |
description |
The cleavage of osteopontin (OPN) by thrombin results in an N-terminal fragment (OPN-N), which exposes a cryptic integrin-binding motif that promotes the adherence of cells, and plays a proinflammatory role. However, the effect of OPN-N on abdominal aortic aneurysm (AAA) remains unknown. The aim of this study was to investigate the expression of OPN-N in aortic tissue samples obtained from patients, who underwent acute aortic dissection (AD), and normal aorta, effect of OPN-N on angiotensin (Ang) II-induced AAA in mice, and relationship between OPN-N and pyroptosis-related inflammatory factors in vitro. Hematoxylin and eosin staining was conducted to detect histological changes. Next, we detected the expression of the OPN-N protein. Additionally, ApoE−/− mice were divided into four groups: control, control + M5Ab (to block the OPN-N function in mice), Ang II, and Ang II + M5Ab. All mice were euthanized after a 28-day infusion and whole aortas, including thoracic and abdominal aortas, were collected for morphological and histological analysis of the AAA. The OPN-N protein expression was higher in patients with AD than in normal individuals, while histological changes in the aortas of Ang II mice were suppressed in Ang II + M5Ab mice. The expression of OPN-N, NOD-, LRR-, and pyrin domain-containing protein 3, pro-Caspase-1, ASC, Gasdermin-d, interleukin (IL)-18, IL-1β, matrix metalloproteinase (MMP) 2, and MMP9 was lower in the Ang II + M5Ab group than in the Ang II group. The gene expression of monocyte chemoattractant protein-1, IL-6, and tumor necrosis factor-α was suppressed in the aortic tissues of the Ang II + M5Ab group compared with the Ang II group. Moreover, the expression of α-smooth muscle actin was lower in the Ang II group than in the Ang II + M5Ab group. In vitro results showed that the increase in the expression of pyroptosis-related inflammatory factors induced by OPN was mediated through the nuclear factor (NF)-κB pathway. In conclusion, OPN-N promotes AAA by increasing the expression of pyroptosis-related inflammatory factors through the NF-κB pathway, inflammation, and extracellular matrix degradation. These results highlight the potential of OPN-N as a new therapeutic target to prevent AAA expansion. |
topic |
osteopontin N-terminal abdominal aortic aneurysm pyroptosis ApoE-/- mice inflammation |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2021.681790/full |
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