Deficiency of Urokinase-Type Plasminogen Activator Receptor Is Associated with the Development of Perivascular Fibrosis in Mouse Heart

Дергилев, К. В.; Белоглазова, И. Б.; Цоколаева, З. И.; Vasilets, Yu. D.; Парфенова, Е. В.

doi:10.1007/s10517-022-05480-9

Cited by 6 publications

(2 citation statements)

References 16 publications

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“…This agreed well with the data showing decreased expression of proangiogenic factors in uPAR−/− cells and suppressed angiogenic secretome activity in vitro and in vivo. Moreover, previously published studies have shown that matrix metalloproteinase (MMP)-12 overexpression cleaves uPAR, impairs angiogenic endothelial cell turnover, and inhibits uPA-mediated angiogenesis thus causing vasculopathy [53][54][55][56][57]. This can be explained by the ability of uPA to protect ECs from apoptosis [58,59] and to promote EC proliferation [60].…”

Section: Discussionmentioning

confidence: 99%

Urokinase-Type Plasminogen Activator Receptor Regulates Prosurvival and Angiogenic Properties of Cardiac Mesenchymal Stromal Cells

Dergilev,

Tsokolaeva,

Goltseva

et al. 2023

IJMS

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One of the largest challenges to the implementation of cardiac cell therapy is identifying selective reparative targets to enhance stem/progenitor cell therapeutic efficacy. In this work, we hypothesized that such a target could be an urokinase-type plasminogen activator receptor (uPAR)—a glycosyl-phosphatidyl-inositol-anchored membrane protein, interacting with urokinase. uPAR is able to form complexes with various transmembrane proteins such as integrins, activating intracellular signaling pathway and thus regulating multiple cell functions. We focused on studying the CD117+ population of cardiac mesenchymal progenitor cells (MPCs), expressing uPAR on their surface. It was found that the number of CD117+ MPCs in the heart of the uPAR−/− mice is lower, as well as their ability to proliferate in vitro compared with cells from wild-type animals. Knockdown of uPAR in CD117+ MPCs of wild-type animals was accompanied by a decrease in survival rate and Akt signaling pathway activity and by an increase in the level of caspase activity in these cells. That suggests the role of uPAR in supporting cell survival. After intramyocardial transplantation of uPAR(−) MPCs, reduced cell retention and angiogenesis stimulation were observed in mice with myocardial infarction model compared to uPAR(+) cells transplantation. Taken together, the present results appear to prove a novel mechanism of uPAR action in maintaining the survival and angiogenic properties of CD117+ MPCs. These results emphasize the importance of the uPAR as a potential pharmacological target for the regulation of reparative properties of myocardial mesenchymal progenitor cells.

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Section: Discussionmentioning

confidence: 99%

Urokinase-Type Plasminogen Activator Receptor Regulates Prosurvival and Angiogenic Properties of Cardiac Mesenchymal Stromal Cells

Dergilev,

Tsokolaeva,

Goltseva

et al. 2023

IJMS

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“…In addition, transplantation of uPA gene attenuates liver fibrosis in liver fibrosis model rats [ 68 ]. uPAR deficiency induces perivascular fibrosis, dermal fibrosis, and pulmonary fibrosis in mice [ 13 , 69 , 70 ] and accelerates renal fibrosis in obstructive nephropathy model mice [ 71 ]. In contrast, suPAR is elevated in focal segmental glomerulosclerosis (FSGS) [ 72 ], and uPAR deficiency attenuates LPS-induced glomerulosclerosis [ 73 ].…”

Section: The Role Of the Upa/upar System In Fibrosismentioning

confidence: 99%

The uPA/uPAR System Orchestrates the Inflammatory Response, Vascular Homeostasis, and Immune System in Fibrosis Progression

Kanno

2023

IJMS

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Fibrotic diseases, such as systemic sclerosis (SSc), idiopathic pulmonary fibrosis, renal fibrosis and liver cirrhosis are characterized by tissue overgrowth due to excessive extracellular matrix (ECM) deposition. Fibrosis progression is caused by ECM overproduction and the inhibition of ECM degradation due to several events, including inflammation, vascular endothelial dysfunction, and immune abnormalities. Recently, it has been reported that urokinase plasminogen activator (uPA) and its receptor (uPAR), known to be fibrinolytic factors, orchestrate the inflammatory response, vascular homeostasis, and immune homeostasis system. The uPA/uPAR system may show promise as a potential therapeutic target for fibrotic diseases. This review considers the role of the uPA/uPAR system in the progression of fibrotic diseases.

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suPAR in cardiovascular disease

Montecillo,

Pirker,

Pemberton

et al. 2024

Advances in Clinical Chemistry

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Deficiency of Urokinase-Type Plasminogen Activator Receptor Is Associated with the Development of Perivascular Fibrosis in Mouse Heart

Cited by 6 publications

References 16 publications

Urokinase-Type Plasminogen Activator Receptor Regulates Prosurvival and Angiogenic Properties of Cardiac Mesenchymal Stromal Cells

Urokinase-Type Plasminogen Activator Receptor Regulates Prosurvival and Angiogenic Properties of Cardiac Mesenchymal Stromal Cells

The uPA/uPAR System Orchestrates the Inflammatory Response, Vascular Homeostasis, and Immune System in Fibrosis Progression

suPAR in cardiovascular disease

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