Endogenously produced hyaluronan contributes to the regulation of peritoneal adhesion development

0583614 - BFÚ 2024 RIV US eng J - Journal Article
Kocurková, Anna - Kerberová, Michaela - Nešporová, K. - Lehka, K. - Sandanusová, Miriam - Simek, M. - Velebný, V. - Kubala, Lukáš - Ambrožová, Gabriela
Endogenously produced hyaluronan contributes to the regulation of peritoneal adhesion development.
Biofactors. Roč. 49, č. 4 (2023), s. 940-955. ISSN 0951-6433. E-ISSN 1872-8081
Institutional support: RVO:68081707
Keywords : mesothelial cells * involvement * glycolysis * activation * prevention * induction * fibrosis
OECD category: Biochemistry and molecular biology
Impact factor: 6, year: 2022
Method of publishing: Open access
https://iubmb.onlinelibrary.wiley.com/doi/10.1002/biof.1957

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
Permanent Link: https://hdl.handle.net/11104/0351622