EUROPEAN JOURNAL OF PHARMACOLOGY
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2024
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IF 4.2
Yuqian Chen,Jin Liu,Qianqian Zhang,Limin Chai,Huan Chen,Danyang Li,Yan Wang,Yuanjie Qiu,Nirui Shen,Jia Zhang,Qingting Wang,Jian Wang,Xinming Xie,Shaojun Li,Manxiang Li
Stromal derived factor 1 (SDF1) has been shown to be involved in the pathogenesis of pulmonary artery hypertension (PAH). However, the detailed molecular mechanisms remain unclear. To address this, we utilized primary cultured rat pulmonary artery smooth muscle cells (PASMCs) and monocrotaline (MCT)-induced PAH rat models to investigate the mechanisms of SDF1 driving PASMCs proliferation and pulmonary arterial remodeling. SDF1 increased runt-related transcription factor 2 (Runx2) acetylation by Calmodulin (CaM)-dependent protein kinase II (CaMKII)-dependent HDAC4 cytoplasmic translocation, elevation of Runx2 acetylation conferred its resistance to proteasome-mediated degradation. The accumulation of Runx2 further upregulated osteopontin (OPN) expression, finally leading to PASMCs proliferation. Blocking SDF1, suppression of CaMKII, inhibition the nuclear export of HDAC4 or silencing Runx2 attenuated pulmonary arterial remodeling and prevented PAH development in MCT-induced PAH rat models. Our study provides novel sights for SDF1 induction of PASMCs proliferation and suggests that targeting SDF1/CaMKII/HDAC4/Runx2 axis has potential value in the management of PAH.
研究领域:
心血管疾病
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2024
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IF 5.4
Yu Han,Li-Hui Sun,Bo Cai,Ming Xia,Chun-Quan Zhu,Dong-Song Li
Large bone defects are a major clinical challenge in bone reconstructive surgery. 3D printing is a powerful technology that enables the manufacture of custom tissue-engineered scaffolds for bone regeneration. Electrical stimulation (ES) is a treatment method for external bone defects that compensates for damaged internal electrical signals and stimulates cell proliferation and differentiation. In this study, we propose a simple, reliable, and versatile strategy to prepare multifunctional 3D printed scaffold combined with ES for bone defect therapy. Firstly, scaffolds composed of polycaprolactone (PCL) and Ti 3 C 2 were prepared by 3D printing technology, and then a stromal cell derived factor 1 (SDF1) containing DOPA tag was loaded onto the scaffold surface. Ti 3 C 2 was selected as the electrode component because of its excellent electrical conductivity. The selection of DOPA-modified SDF-1(DOPA-SDF1) can improve the material binding ability and exert long-term stem cell recruitment function. The results show that prepared 3D printed scaffold (DOPA-SDF1@PCL#Ti 3 C 2 ) has good hydrophilicity, electrical conductivity, antibacterial property, biocompatibility and stem cell recruitment ability. Furthermore, the expression of osteogenic specific genes in scaffold surface cells was significantly increased when pulse ES (PES) treatment was applied. The results of tibial plateau defect repair experiment showed that DOPA-SDF1@PCL#Ti 3 C 2 scaffold can significantly promote the formation of new bone and collagen fibres. When the DOPA-SDF1@PCL#Ti 3 C 2 scaffold was used in combination with PES therapy, the bone defect regeneration rate was further improved. This kind of scaffold could provide a new strategy for promoting the healing of large bone injuries and could expand the application of adjuvant therapy such as PES.
研究领域:
组织工程
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生物材料
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再生医学
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生物医学工程
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Communication and Signaling
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2023
·Vol. 21
·期 1
·1-17
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IF 8.4
Zhao Weiming,Wang Lan,Yang Juntang,Chen Xinyu,Guo Xiaoshu,Xu Kai,Wang Ningdan,Zhao Wenyu,Xia Cong,Lian Hui,Rosas Ivan,Yu Guoying
Background Matrix metalloproteinases (MMPs) play important roles in remodeling the extracellular matrix and in the pathogenesis of idiopathic pulmonary fibrosis (IPF). MMP19, which is an MMP, was significantly upregulated in hyperplastic alveolar epithelial cells in IPF lung tissues and promoted epithelial-mesenchymal transition (EMT). Recent studies have demonstrated that endothelial-to-mesenchymal transition (E(nd)MT) contributes to pulmonary fibrosis. However, the role of MMP19 in pulmonary vascular injury and repair and E(nd)MT remains unclear. Methods To determine the role of MMP19 in E(nd)MT and pulmonary fibrosis. MMP19 expressions were determined in the lung endothelial cells of IPF patients and bleomycin (BLM)-induced mice. The roles of MMP19 in E(nd)MT and endothelial barrier permeability were studied in the MMP19 cDNA-transfected primary human pulmonary microvascular endothelial cells (HPMECs) and MMP19 adenoassociated virus (MMP19-AAV)-infected mice. The regulatory mechanism of MMP19 in pulmonary fibrosis was elucidated by blocking its interacting proteins SDF1 and ET1 with AMD3100 and Bosentan, respectively. Results In this study, we found that MMP19 expression was significantly increased in the lung endothelial cells of IPF patients and BLM-induced mice compared to the control groups. MMP19 promoted E(nd)MT and the migration and permeability of HPMECs in vitro, stimulated monocyte infiltration into the alveolus, and aggravated BLM-induced pulmonary fibrosis in vivo. SDF1 and Endothelin-1 (ET1) were physically associated with MMP19 in HPMECs and colocalized with MMP19 in endothelial cells in IPF patient lung tissues. AMD3100 and bosentan alleviated the fibrosis induced by MMP19 in the BLM mouse model. Conclusion MMP19 promoted E(nd)MT by interacting with ET1 and stimulated monocyte infiltration into lung tissues via the SDF1/CXCR4 axis, thus aggravating BLM-induced pulmonary fibrosis. Vascular integrity regulated by MMP19 could be a promising therapeutic target for suppressing pulmonary fibrosis.
Video abstract
研究领域:
呼吸病学
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细胞生物学
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2019
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IF 3.973
Xinkun Shen,Yonglin Yu,Pingping Ma,Zhong Luo,Yan Hu,Menghuan Li,Ye He,Yangyang Zhang,Zhihong Peng,Guanbin Song,Kaiyong Cai
Before mesenchymal stem cells (MSCs) adhere to the surface of an implant and differentiate into osteoblasts, monocytes (especially macrophages) arrive at the bone injury site and interact with the implant and subsequent MSCs. In our previous study, large titania nanotubes (TNT 110 ) had been verified to endow superior oxidation resistance to osteoblasts. The early regulation between macrophages and MSCs by surface nanotubes under oxidative stress (OS) was evaluated further in this study. Cellular and molecular results show that TNT 110 greatly increased early inflammation of macrophages by activating integrin/FAK-mediated MAPK and NFκB signals and simultaneously promoted their gene expression of SDF1, IL-8, and CCL2 (chemokines) compared with 30 nm nanotubes and titanium substrates. Co-culture results show that more MSCs were recruited by those chemokines and may promote osteogenic self-differentiation, reducing early inflammation of macrophages by accelerating their M1-to-M2 transition in the TNT 110 group. All findings reveal that the early cellular behavior of macrophages and MSCs was effectively regulated by TNT 110 , indicating large nanotubes would be more suitable to prevent oxidative damages.
研究领域:
生物材料
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细胞生物学
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）