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@article{2294357,
author = {Kocurková, Anna and Kerberova, Michaela and Nesporova, Kristina and Lehka, Katerina and Sandanusová, Miriam and Simek, Matej and Velebny, Vladimir and Kubala, Lukáš and Ambrozova, Gabriela},
article_number = {4},
doi = {http://dx.doi.org/10.1002/biof.1957},
keywords = {fibrosis; hyaluronic acid; mesothelial cells; metabolism; peritoneal adhesions},
language = {eng},
issn = {0951-6433},
journal = {Biofactors},
title = {Endogenously produced hyaluronan contributes to the regulation of peritoneal adhesion development},
url = {https://doi.org/10.1002/biof.1957},
volume = {49},
year = {2023}
}
TY - JOUR
ID - 2294357
AU - Kocurková, Anna - Kerberova, Michaela - Nesporova, Kristina - Lehka, Katerina - Sandanusová, Miriam - Simek, Matej - Velebny, Vladimir - Kubala, Lukáš - Ambrozova, Gabriela
PY - 2023
TI - Endogenously produced hyaluronan contributes to the regulation of peritoneal adhesion development
JF - Biofactors
VL - 49
IS - 4
SP - 940-955
EP - 940-955
PB - Wiley
SN - 09516433
KW - fibrosis
KW - hyaluronic acid
KW - mesothelial cells
KW - metabolism
KW - peritoneal adhesions
UR - https://doi.org/10.1002/biof.1957
N2 - Peritoneal adhesions are postsurgical fibrotic complications connected to peritoneal inflammation. The exact mechanism of development is unknown; however, an important role is attributed to activated mesothelial cells (MCs) overproducing macromolecules of extracellular matrix (ECM), including hyaluronic acid (HA). It was suggested that endogenously-produced HA contributes to the regulation of different fibrosis-related pathologies. However, little is known about the role of altered HA production in peritoneal fibrosis. We focused on the consequences of the increased turnover of HA in the murine model of peritoneal adhesions. Changes of HA metabolism were observed in early phases of peritoneal adhesion development in vivo. To study the mechanism, human MCs MeT-5A and murine MCs isolated from the peritoneum of healthy mice were pro-fibrotically activated by transforming growth factor beta (TGF beta), and the production of HA was attenuated by two modulators of carbohydrate metabolism, 4-methylumbelliferone (4-MU) and 2-deoxyglucose (2-DG). The attenuation of HA production was mediated by upregulation of HAS2 and downregulation of HYAL2 and connected to the lower expression of pro-fibrotic markers, including fibronectin and a-smooth muscle actin (alpha SMA). Moreover, the inclination of MCs to form fibrotic clusters was also downregulated, particularly in 2-DG-treated cells. The effects of 2-DG, but not 4-MU, were connected to changes in cellular metabolism. Importantly, the inhibition of AKT phosphorylation was observed after the use of both HA production inhibitors. In summary, we identified endogenous HA as an important
ER -
KOCURKOVÁ, Anna, Michaela KERBEROVA, Kristina NESPOROVA, Katerina LEHKA, Miriam SANDANUSOVÁ, Matej SIMEK, Vladimir VELEBNY, Lukáš KUBALA a Gabriela AMBROZOVA. Endogenously produced hyaluronan contributes to the regulation of peritoneal adhesion development. \textit{Biofactors}. Wiley, 2023, roč.~49, č.~4, s.~940-955. ISSN~0951-6433. Dostupné z: https://dx.doi.org/10.1002/biof.1957.
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