Type V Collagen in Scar Tissue Regulates the Size of Scar after Heart Injury

Yokota, Tomohiro; McCourt, Jackie L; Ma, Feiyang; Ren, Shuxun; Shen, Li; Kim, Tae-Hyung; Kurmangaliyev, Yerbol Z.; Nasiri, Rohollah; Ahadian, Samad; Nguyen, Thang L.; Tan, Xing Haw Marvin; Zhou, Yonggang; Wu, Rimao; Rodriguez, Abraham; Cohn, Whitaker; Wang, Yibin; Whitelegge, Julian P.; Ryazantsev, Sergey; Khademhosseini, Ali; Teitell, Michael A.; Chiou, Pei-Yu; Birk, David E.; Rowat, Amy C.; Crosbie, Rachelle H.; Pellegrini, Matteo; Seldin, Marcus M.; Lusis, Aldons J.; Deb, Arjun

doi:10.1016/j.cell.2020.06.030

Cited by 134 publications

(111 citation statements)

References 66 publications

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“…Studies have also shown that both collagen receptor integrin and hyaluronan acid receptor CD44 are involved in the mechanical conduction of ECM stiffness ( 13 ). Specifically, hyaluronan acid with different molecular weights binds to its receptor CD44, whereas collagen components of various subtypes bind to corresponding integrin receptor subtypes, regulating downstream signal pathways and producing different biological effects ( Table 1 ).…”

Section: Extracellular Matrix Components and Mechanical Biological Comentioning

confidence: 99%

Extracellular Matrix Stiffness: New Areas Affecting Cell Metabolism

Tian

Pei

et al. 2021

Front. Oncol.

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In recent years, in-depth studies have shown that extracellular matrix stiffness plays an important role in cell growth, proliferation, migration, immunity, malignant transformation, and apoptosis. Most of these processes entail metabolic reprogramming of cells. However, the exact mechanism through which extracellular matrix stiffness leads to metabolic reprogramming remains unclear. Insights regarding the relationship between extracellular matrix stiffness and metabolism could help unravel novel therapeutic targets and guide development of clinical approaches against a myriad of diseases. This review provides an overview of different pathways of extracellular matrix stiffness involved in regulating glucose, lipid and amino acid metabolism.

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Section: Extracellular Matrix Components and Mechanical Biological Comentioning

confidence: 99%

Extracellular Matrix Stiffness: New Areas Affecting Cell Metabolism

Tian

Pei

et al. 2021

Front. Oncol.

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“…Besides, the histopathological features of skin and lung in a animal model of systemic sclerosis induced by type V collagen revealed that increased collagen V fibers and COL5A1 gene expression ( Teodoro et al, 2019 ). The study by Yokota et al (2020) demonstrated that type V collagen played a crucial role in scar size following myocardial infarction and induced fibroblast activation. Therefore, based on the regulatory role of COL5A1 in these fibrosis diseases, it could be speculated that COL5A1 might be associated with the pathogenesis of keloids and have the potential to serve as a novel therapeutic target.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA CircCOL5A1 Sponges the MiR-7-5p/Epac1 Axis to Promote the Progression of Keloids Through Regulating PI3K/Akt Signaling Pathway

Liu

Zhang

et al. 2021

Front. Cell Dev. Biol.

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Keloids, as a result of abnormal wound healing in susceptible individuals, are characterized by the hyper-proliferation of fibroblasts and exaggerated deposition of extracellular matrix. Current surgical and therapeutic modalities provide limited satisfactory results. Growing evidence has highlighted the roles of circRNAs in acting as miRNA sponges. However, up to date, the regulatory mechanism of circRNAs in the pathological process of keloids has rarely been reported. In this study, cell proliferation, cell migration, flow cytometry, western blotting, fluorescence in situ hybridization, dual-luciferase activity, and immunohistochemistry assays were applied to explore the roles and mechanisms of the circCOL5A1/miR-7-5p/Epac1 axis in the keloid. The therapeutic potential of circCOL5A1 was investigated by establishing keloid implantation models. The RT-qPCR result revealed that circCOL5A1 expression was obviously higher in keloid tissues and keloid fibroblasts. Subsequent cellular experiments demonstrated that circCOL5A1 knockdown repressed the proliferation, migration, extracellular matrix (ECM) deposition, whereas promoted cell apoptosis, through the PI3K/Akt signaling pathway. Furthermore, RNA-fluorescence in situ hybridization (RNA-FISH) illustrated that both circCOL5A1 and miR-7-5p were located in the cytoplasm. The luciferase reporter gene assay confirmed that exact binding sites were present between circCOL5A1 and miR-7-5p, as well as between miR-7-5p and Epac1. Collectively, the present study revealed that circCOL5A1 functioned as competing endogenous RNA (ceRNA) by adsorbing miR-7-5p to release Epac1, which contributed to pathological hyperplasia of keloids through activating the PI3K/Akt signaling pathway. Our data indicated that circCOL5A1 might serve as a novel promising therapeutic target and represent a new avenue to understand underlying pathogenesis for keloids.

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“…Based on in situ hybridization analysis, Roulet's group reported that the expression of COL5A1 plays an important role in the development of functional connective tissues, especially in the heart, dorsal aorta wall, skin, and vertebral column, suggesting that COL5A1 plays an important role in the development of these organs in developing embryos (Roulet et al, 2007). Interestingly, Yokota et al (2020) found that the COL5A1 expression level significantly correlated with scar size after myocardial infarction mechanically, not only in the regulation of the size of cardiac scars but also in tissue mechanical properties in an integrin-dependent manner. The expression level of B2M in the plasma is not simply a significant marker for kidney injury but a novel regulator involved in heart failure and heart remodeling (Vianello et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Single-Cell RNA Sequencing and Quantitative Proteomics Analysis Elucidate Marker Genes and Molecular Mechanisms in Hypoplastic Left Heart Patients With Heart Failure

Zhou

Zou

et al. 2021

Front. Cell Dev. Biol.

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ObjectiveTo probe markers and molecular mechanisms of the hypoplastic left heart (HLH) by single-cell RNA sequencing (scRNA-seq) and quantitative proteomics analysis.MethodsFollowing data preprocessing, scRNA-seq data of pluripotent stem cell (iPSC)-derived cardiomyocytes from one HLH patient and one control were analyzed by the Seurat package in R. Cell clusters were characterized, which was followed by a pseudotime analysis. Markers in the pseudotime analysis were utilized for functional enrichment analysis. Quantitative proteomics analysis was based on peripheral blood samples from HLH patients without heart failure (HLH-NHF), HLH patients with heart failure (HLH-HF), and healthy controls. Hub genes were identified by the intersection of pseudotime markers and differentially expressed proteins (DE-proteins), which were validated in the GSE77798 dataset, RT-qPCR, and western blot.ResultsCardiomyocytes derived from iPSCs were clustered into mesenchymal stem cells, myocardium, and fibroblast cells. Pseudotime analysis revealed their differentiation trajectory. Markers in the three pseudotime clusters were significantly associated with distinct biological processes and pathways. Finally, three hub genes (MMP2, B2M, and COL5A1) were identified, which were highly expressed in the left (LV) and right (RV) ventricles of HLH patients compared with controls. Furthermore, higher expression levels were detected in HLH patients with or without HF than in controls.ConclusionOur findings elucidate marker genes and molecular mechanisms of HLH, deepening the understanding of the pathogenesis of HLH.

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Type V Collagen in Scar Tissue Regulates the Size of Scar after Heart Injury

Cited by 134 publications

References 66 publications

Extracellular Matrix Stiffness: New Areas Affecting Cell Metabolism

Extracellular Matrix Stiffness: New Areas Affecting Cell Metabolism

Circular RNA CircCOL5A1 Sponges the MiR-7-5p/Epac1 Axis to Promote the Progression of Keloids Through Regulating PI3K/Akt Signaling Pathway

Single-Cell RNA Sequencing and Quantitative Proteomics Analysis Elucidate Marker Genes and Molecular Mechanisms in Hypoplastic Left Heart Patients With Heart Failure

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