Midkine Prevents Calcification of Aortic Valve Interstitial Cells via Intercellular Crosstalk

Zhou, Qian; Cao, Hong; Hang, Xiaoyi; Liang, Huamin; Zhu, Miaomiao; Fan, Yixian; Shi, Jing; Dong, Nianguo; He, Ximiao

doi:10.3389/fcell.2021.794058

Cited by 7 publications

(7 citation statements)

References 58 publications

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“…These interactions have various functions, such as angiogenesis, oncogenesis, stem cell self-renewal, and play important roles in the regeneration of tissues, such as the myocardium, cartilage, neuron, muscle, and bone 51 . Studies have shown that midkine impedes the calcification of aortic valve interstitial cells through cell-cell communications 52 . In addition, SDC2 is found required for migration of the bilateral heart fields towards the mid-line in zebrafish model 53 .…”

Section: Resultsmentioning

confidence: 99%

Identifying multicellular spatiotemporal organization of cells with SpaceFlow

et al. 2022

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One major challenge in analyzing spatial transcriptomic datasets is to simultaneously incorporate the cell transcriptome similarity and their spatial locations. Here, we introduce SpaceFlow, which generates spatially-consistent low-dimensional embeddings by incorporating both expression similarity and spatial information using spatially regularized deep graph networks. Based on the embedding, we introduce a pseudo-Spatiotemporal Map that integrates the pseudotime concept with spatial locations of the cells to unravel spatiotemporal patterns of cells. By comparing with multiple existing methods on several spatial transcriptomic datasets at both spot and single-cell resolutions, SpaceFlow is shown to produce a robust domain segmentation and identify biologically meaningful spatiotemporal patterns. Applications of SpaceFlow reveal evolving lineage in heart developmental data and tumor-immune interactions in human breast cancer data. Our study provides a flexible deep learning framework to incorporate spatiotemporal information in analyzing spatial transcriptomic data.

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Section: Resultsmentioning

confidence: 99%

Identifying multicellular spatiotemporal organization of cells with SpaceFlow

et al. 2022

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“…A study of CAVD disclosed that aortic matrix valvular interstitial cells (VICs) significantly expressed MK, which in a paracrine manner acted on activated and complement-activated VICs to prohibit calcification ( 116 ). Congruently, the addition of MK to the osteogenic media of VICs, isolated from aortic valve tissue from non-CAVD patients, hindered calcification ( 116 ). The expression of RUNX2 and ALP, markers of osteogenic differentiation in VICs, was diminished upon MK treatment ( 116 ).…”

Section: Discussion: Midkine In Cardiovascular Diseasesmentioning

confidence: 99%

“…Congruently, the addition of MK to the osteogenic media of VICs, isolated from aortic valve tissue from non-CAVD patients, hindered calcification ( 116 ). The expression of RUNX2 and ALP, markers of osteogenic differentiation in VICs, was diminished upon MK treatment ( 116 ). Hence, MK partakes in the inhibition of VIC osteogenic differentiation and could hereby protect against CAVD development via mediating intercellular crosstalk ( 116 ).…”

Section: Discussion: Midkine In Cardiovascular Diseasesmentioning

confidence: 99%

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Midkine—A novel player in cardiovascular diseases

Majaj

Weckbach

2022

Front. Cardiovasc. Med.

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Midkine (MK) is a 13-kDa heparin-binding cytokine and growth factor with anti-apoptotic, pro-angiogenic, pro-inflammatory and anti-infective functions, that enable it to partake in a series of physiological and pathophysiological processes. In the past, research revolving around MK has concentrated on its roles in reproduction and development, tissue protection and repair as well as inflammatory and malignant processes. In the recent few years, MK's implication in a wide scope of cardiovascular diseases has been rigorously investigated. Nonetheless, there is still no broadly accepted consensus on whether MK exerts generally detrimental or favorable effects in cardiovascular diseases. The truth probably resides somewhere in-between and depends on the underlying physiological or pathophysiological condition. It is therefore crucial to thoroughly examine and appraise MK's participation in cardiovascular diseases. In this review, we introduce the MK gene and protein, its multiple receptors and signaling pathways along with its expression in the vascular system and its most substantial functions in cardiovascular biology. Further, we recapitulate the current evidence of MK's expression in cardiovascular diseases, addressing the various sources and modes of MK expression. Moreover, we summarize the most significant implications of MK in cardiovascular diseases with particular emphasis on MK's advantageous and injurious functions, highlighting its ample diagnostic and therapeutic potential. Also, we focus on conflicting roles of MK in a number of cardiovascular diseases and try to provide some clarity and guidance to MK's multifaceted roles. In summary, we aim to pave the way for MK-based diagnostics and therapies that could present promising tools in the diagnosis and treatment of cardiovascular diseases.

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“…Currently, immune cells are also believed to play important roles in aortic valve calcification ( 12 – 14 ). Zhou’s study ( 15 ) showed that immune cells accounted for about 5.4% in the aortic valve tissue, and macrophages were the most dominant immune cells. Another study showed that ( 16 ) in the calcified aortic valves, the infiltration of M1 macrophages was increased, while the infiltration of M2 macrophages was decreased.…”

Section: Introductionmentioning

confidence: 99%

Shared gene characteristics and molecular mechanisms of macrophages M1 polarization in calcified aortic valve disease

Qin

Chen²,

Li³

et al. 2023

Front. Cardiovasc. Med.

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BackgroundCAVD is a common cardiovascular disease, but currently there is no drug treatment. Therefore, it is urgent to find new and effective drug therapeutic targets. Recent evidence has shown that the infiltration of M1 macrophages increased in the calcified aortic valve tissues, but the mechanism has not been fully elucidated. The purpose of this study was to explore the shared gene characteristics and molecular mechanisms of macrophages M1 polarization in CAVD, in order to provide a theoretical basis for new drugs of CAVD.MethodsThe mRNA datasets of CAVD and M1 polarization were downloaded from Gene Expression Omnibus (GEO) database. R language, String, and Cytoscape were used to analyze the functions and pathways of DEGs and feature genes. Immunohistochemical staining and Western Blot were performed to verify the selected hub genes.ResultsCCR7 and GZMB were two genes appeared together in hub genes of M1-polarized and CAVD datasets that might be involved in the process of CAVD and macrophages M1 polarization. CCR7 and CD86 were significantly increased, while CD163 was significantly decreased in the calcified aortic valve tissues. The infiltration of M1 macrophages was increased, on the contrary, the infiltration of M2 macrophages was decreased in the calcified aortic valve tissues.ConclusionThis study reveals the shared gene characteristics and molecular mechanisms of CAVD and macrophages M1 polarization. The hub genes and pathways we found may provide new ideas for the mechanisms underlying the occurrence of M1 polarization during CAVD process.

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Midkine Prevents Calcification of Aortic Valve Interstitial Cells via Intercellular Crosstalk

Cited by 7 publications

References 58 publications

Identifying multicellular spatiotemporal organization of cells with SpaceFlow

Identifying multicellular spatiotemporal organization of cells with SpaceFlow

Midkine—A novel player in cardiovascular diseases

Shared gene characteristics and molecular mechanisms of macrophages M1 polarization in calcified aortic valve disease

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