Dataset Information

Endothelial cell?derived CCL15 mediates the transmigration of fibrocytes through the CCL15?CCR1 axis in vitro.

ABSTRACT: Wound healing is a complex physiological process in which fibrocytes serve a vital role. However, the mechanism underlying the recruitment of fibrocytes during wound healing remains largely unknown. The present study aimed to investigate whether endothelial cells are involved in the recruitment of fibrocytes in wound healing. To mimic the in vivo angiogenic process, a co?culture system consisting of endothelial cells and fibrocytes was achieved using a permeable Transwell co?culture system. The expression of chemokines produced by endothelial cells with or without co?culture was then measured using a gene chip. Based on the dataset from chip analysis, chemokine ligand 15 (CCL15) produced by endothelial cells was identified, which likely serves a regulatory role in mediating the transmigration of fibrocytes. Overexpression of CCL15 in endothelial cells or chemokine receptor 1 (CCR1) in fibrocytes promoted the transmigration of fibrocytes, whilst silencing the expression of CCL15 in endothelial cells or that of CCR1 in fibrocytes attenuated the transmigration of fibrocytes. Results from the present study suggested that the CCL15?CCR1 axis between endothelial cells and fibrocytes serves a vital role in mediating the recruitment of fibrocytes during wound healing.

SUBMITTER: Pang N

PROVIDER: S-EPMC7647002 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Endothelial cell‑derived CCL15 mediates the transmigration of fibrocytes through the CCL15‑CCR1 axis in vitro.

Pang Nan N Lin Zhixiao Z Wang Xiaolin X Xu Lirong L Xu Xiaoli X Huang Rong R Li Xingxing X Li Xueyong X Li Jinqing J

Molecular medicine reports 20201019 6

Wound healing is a complex physiological process in which fibrocytes serve a vital role. However, the mechanism underlying the recruitment of fibrocytes during wound healing remains largely unknown. The present study aimed to investigate whether endothelial cells are involved in the recruitment of fibrocytes in wound healing. To mimic the in vivo angiogenic process, a co‑culture system consisting of endothelial cells and fibrocytes was achieved using a permeable Transwell co‑culture system. The ...[more]

PMID: 33174007

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Project description:Hyperglycemia is reported to accelerate endothelial cell senescence that contributes to diabetic complications. The underlying mechanism, however, remains elusive. We previously demonstrated AQR as a susceptibility gene for type 2 diabetes mellitus (T2DM) and showed that it was increased in multiple tissues in models with T2DM or metabolic syndrome. This study aimed to investigate the role of AQR in hyperglycemia-induced senescence and its underlying mechanism. Here, we retrieved several datasets of the aging models and found the expression of AQR was increased by high glucose and by aging across species, including C. elegans (whole-body), rat (cardiac tissues), and monkey (blood). we validated the increased AQR expression in senescent human umbilical vein endothelial cells (HUVECs). When overexpressed, AQR promoted the endothelial cell senescence, confirmed by an increased number of cells stained with senescence-associated beta-galactosidase and upregulation of CDKN1A (P21) as well as the prohibited cellular colony formation and G2/M phase arrest. To explore the mechanism by which AQR regulated the cellular senescence, transcriptomic analyses of HUVECs with the overexpression and knockdown of the AQR were performed. We identified 52 co-expressed genes that were enriched, in the terms of plasminogen activation, innate immunity, immunity, and antiviral defense. Among co-expressed genes, PLAU was selected to evaluate its contribution to senescence for its highest strength in the enrichment of the biological process. We demonstrated that the knockdown of PLAU rescued senescence-related phenotypes, endothelial cell activation, and inflammation in models induced by AQR or TNF-α. These findings, for the first time, indicate that AQR/PLAU is a critical signaling axis in the modulation of endothelial cell senescence, revealing a novel link between hyperglycemia and vascular dysfunction. The study may have implications in the prevention of premature vascular aging associated with T2DM.

Dataset Information

Endothelial cell?derived CCL15 mediates the transmigration of fibrocytes through the CCL15?CCR1 axis in vitro.

Publications

Endothelial cell‑derived CCL15 mediates the transmigration of fibrocytes through the CCL15‑CCR1 axis in vitro.

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