KOCURKOVÁ, Anna, Michaela KERBEROVA, Kristina NESPOROVA, Katerina LEHKA, Miriam SANDANUSOVÁ, Matej SIMEK, Vladimir VELEBNY, Lukáš KUBALA and Gabriela AMBROZOVA. Endogenously produced hyaluronan contributes to the regulation of peritoneal adhesion development. Biofactors. Wiley, 2023, vol. 49, No 4, p. 940-955. ISSN 0951-6433. Available from: https://dx.doi.org/10.1002/biof.1957.
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Basic information
Original name Endogenously produced hyaluronan contributes to the regulation of peritoneal adhesion development
Authors KOCURKOVÁ, Anna (203 Czech Republic, belonging to the institution), Michaela KERBEROVA, Kristina NESPOROVA, Katerina LEHKA, Miriam SANDANUSOVÁ (703 Slovakia, belonging to the institution), Matej SIMEK, Vladimir VELEBNY, Lukáš KUBALA (203 Czech Republic, belonging to the institution) and Gabriela AMBROZOVA (guarantor).
Edition Biofactors, Wiley, 2023, 0951-6433.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10608 Biochemistry and molecular biology
Country of publisher United States of America
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 6.000 in 2022
RIV identification code RIV/00216224:14310/23:00131093
Organization unit Faculty of Science
Doi http://dx.doi.org/10.1002/biof.1957
UT WoS 000983044700001
Keywords in English fibrosis; hyaluronic acid; mesothelial cells; metabolism; peritoneal adhesions
Tags rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Marie Šípková, DiS., učo 437722. Changed: 25/10/2023 11:41.
Abstract
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
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