Dokument: Funktionelle Relevanz der Extrazellulären Matrixmoleküle Periostin und Tenascin C in Leberschädigung und -regeneration
| Titel: | Funktionelle Relevanz der Extrazellulären Matrixmoleküle Periostin und Tenascin C in Leberschädigung und -regeneration | |||||||
| Weiterer Titel: | The functional relevance of the extracellular matrix molecules Periostin and Tenascin C in liver damage and regeneration | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=63557 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20230905-180554-9 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Deutsch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Nguyen, Tra My [Autor] | |||||||
| Dateien: |
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| Beitragende: | Univ.-Prof. Dr. Esposito, Irene [Gutachter] Prof. Dr. med. Keitel-Anselmino, Verena [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibungen: | Die besondere Regenerationsfähigkeit der Leber gewinnt wegen steigender Inzidenzen der chronischen Lebererkrankungen an Bedeutung. Die Rolle der extrazellulären Matrixproteine Periostin (POSTN) und Tenascin C (TNC) bei der Leberregeneration auftretenden duktulären Reaktion ist noch unzureichend untersucht. Das Ziel dieser Arbeit war die Prüfung möglicher Zusammenhänge der Expression von POSTN und TNC mit pathophysiologischen Parametern, sowie die Untersuchung eines Einflusses auf die Aktivierung und Expansion von hepatischen Progenitorzellen.
Dazu wurden 151 humane Gewebeproben mit chronischer Leberschädigung untersucht und entsprechend ihres Fibrosegrades und ihrer histologischen Diagnose klassifiziert. Immunhistochemische Färbungen waren die Basis für die Untersuchung der Expression von POSTN, TNC und der hepatischen Progenitorzellen (EpCAM, SOX9, AFP, NCAM, CK7/CK19) und Stellatumzellen (NCAM, αSMA, Synaptophysin, Desmin). Die Studienergebnisse zeigen, dass TNC und POSTN in der gesunden Leber nur äußerst schwach bis gar nicht, jedoch bei den Prozessen der Leberschädigung und -regeneration vermehrt exprimiert werden. Abhängig von der Ätiologie der Leberschädigung werden TNC und POSTN unterschiedlich stark exprimiert. Bei Fortschreiten des Krankheitsstadiums (Desmet 3 und 4) nimmt die (peri-) portale und (peri-) septale Expression von TNC und POSTN signifikant zu (p < 0,001 bzw. p < 0,05). Die (peri-) portale und (peri-) septale Expression von TNC und POSTN korreliert zudem signifikant mit der Proliferation hepatischer Progenitorzellen bei der Leberregeneration (duktuläre Reaktion) (jeweils p < 0,001) sowie mit der Aktivierung von hepatischen Stellatumzellen (p < 0,001 für TNC, p = 0,002 für POSTN). Die heterogene Expression von TNC und POSTN im geschädigten Lebergewebe, sowie die Korrelation der Markerexpression mit der Aktivierung von hepatischen Stellatumzellen und der Proliferation von hepatischen Progenitorzellen, weist auf eine aktive Rolle der beiden extrazellulären Matrixproteine in der Leberschädigung und -regeneration hin.The special regenerative capacity of the liver is becoming increasingly important due to the rising incidences of chronic liver diseases. The role of the extracellular matrix proteins periostin (POSTN) and tenascin C (TNC) in the ductal response occurring during liver regeneration is still poorly understood. The aim of this work was therefore to test possible correlations of POSTN and TNC expression with pathophysiological parameters, as well as to examine an influence of the two proteins on the activation and expansion of hepatic progenitor cells. For this purpose, 151 human tissue samples with chronic liver injury were examined and classified according to their degree of fibrosis and histological diagnosis. Immunohistochemical staining provided the basis for studying the expression of POSTN, TNC, and hepatic progenitor cells (EpCAM, SOX9, AFP, NCAM, CK7/CK19) and stellate cells (NCAM, αSMA, Synaptophysin, Desmin). The study results show that TNC and POSTN are expressed very weakly to not at all in the healthy liver but are expressed more abundantly in the processes surrounding liver injury and regeneration. POSTN and TNC are expressed differently depending on the aetiology of liver injury. As disease stage progresses (Desmet 3 and 4), (peri-) portal and (peri-) septal expression of TNC and POSTN increases significantly (p < 0.001 and p < 0.05, respectively). The (peri-) portal and (peri-) septal expression of TNC and POSTN also correlated significantly with the proliferation of hepatic progenitor cells in liver regeneration (ductal response) (p < 0.001 each) and with the activation of hepatic stellate cells (p < 0.001 for TNC, p = 0.002 for POSTN). From these results, we conclude that the heterogeneous expression of TNC and POSTN in damaged liver tissue and the correlation of marker expression with hepatic stellate cell activation and hepatic progenitor cell proliferation indicate an active role of the two extracellular matrix proteins in liver injury and regeneration. | |||||||
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| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät » Institute » Institut für Pathologie | |||||||
| Dokument erstellt am: | 05.09.2023 | |||||||
| Dateien geändert am: | 05.09.2023 | |||||||
| Promotionsantrag am: | 02.03.2022 | |||||||
| Datum der Promotion: | 31.08.2023 |
