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Status: Bibliographieeintrag

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Verfasst von:Schmaus, Anja [VerfasserIn]   i
 Rothley, Melanie [VerfasserIn]   i
 Schreiber, Caroline [VerfasserIn]   i
 Möller, Stephanie [VerfasserIn]   i
 Roßwag, Sven [VerfasserIn]   i
 Franz, Sandra [VerfasserIn]   i
 Garvalov, Boyan K. [VerfasserIn]   i
 Thiele, Wilko [VerfasserIn]   i
 Spataro, Sofia [VerfasserIn]   i
 Herskind, Carsten [VerfasserIn]   i
 Prunotto, Marco [VerfasserIn]   i
 Anderegg, Ulf [VerfasserIn]   i
 Schnabelrauch, Matthias [VerfasserIn]   i
 Sleeman, Jonathan P. [VerfasserIn]   i
Titel:Sulfated hyaluronic acid inhibits the hyaluronidase CEMIP and regulates the HA metabolism, proliferation and differentiation of fibroblasts
Verf.angabe:Anja Schmaus, Melanie Rothley, Caroline Schreiber, Stephanie Möller, Sven Roßwag, Sandra Franz, Boyan K. Garvalov, Wilko Thiele, Sofia Spataro, Carsten Herskind, Marco Prunotto, Ulf Anderegg, Matthias Schnabelrauch and Jonathan Sleeman
E-Jahr:2022
Jahr:May 2022
Umfang:19 S.
Fussnoten:Online verfügbar: 8. April 2022, Artikelversion: 25. April 2022 ; Gesehen am 11.03.2024
Titel Quelle:Enthalten in: Matrix biology
Ort Quelle:Amsterdam [u.a.] : Elsevier, 1994
Jahr Quelle:2022
Band/Heft Quelle:109(2022) vom: Mai, Seite 173-191
ISSN Quelle:1569-1802
Abstract:Hyaluronan (HA) is an extracellular matrix component that regulates a variety of physiological and pathological processes. The function of HA depends both on its overall amount and on its size, properties that are controlled by HA synthesizing and degrading enzymes. The lack of inhibitors that can specifically block individual HA degrading enzymes has hampered attempts to understand the contribution of individual hyaluronidases to different physiological and pathological processes. CEMIP is a recently discovered hyaluronidase that cleaves HA through mechanisms and under conditions that are distinct from those of other hyaluronidases such as HYAL1 or HYAL2. The role of its hyaluronidase activity in physiology and disease is poorly understood. Here, we characterized a series of sulfated HA derivatives (sHA) with different sizes and degrees of sulfation for their ability to inhibit specific hyaluronidases. We found that highly sulfated sHA derivatives potently inhibited CEMIP hyaluronidase activity. One of these compounds, designated here as sHA3.7, was characterized further and shown to inhibit CEMIP with considerable selectivity over other hyaluronidases. Inhibition of CEMIP with sHA3.7 in fibroblasts, which are the main producers of HA in the interstitial matrix, increased the cellular levels of total and high molecular weight HA, while decreasing the fraction of low molecular weight HA fragments. Genetic deletion of CEMIP in mouse embryonic fibroblasts (MEFs) produced analogous results and confirmed that the effects of sHA3.7 on HA levels were mediated by CEMIP inhibition. Importantly, both CEMIP deletion and its inhibition by sHA3.7 suppressed fibroblast proliferation, while promoting differentiation into myofibroblasts, as reflected in a lack of CEMIP in myofibroblasts within skin wounds in experimental mice. By contrast, adipogenic and osteogenic differentiation were attenuated upon CEMIP loss or inhibition. Our results demonstrate the importance of CEMIP for the HA metabolism, proliferation and differentiation of fibroblasts, and suggest that inhibition of CEMIP with sulfated HA derivatives such as sHA3.7 has potential utility in pathological conditions that are dependent on CEMIP function.
DOI:doi:10.1016/j.matbio.2022.04.001
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1016/j.matbio.2022.04.001
 Volltext: https://www.sciencedirect.com/science/article/pii/S0945053X22000531
 DOI: https://doi.org/10.1016/j.matbio.2022.04.001
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:CEMIP
 fibroblast
 Hyaluronan (HA)
 hyaluronidase
 KIAA1199
 sulfated HA
K10plus-PPN:1883054281
Verknüpfungen:→ Zeitschrift

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