Role of WNT1-inducible signaling pathway protein-1 (WISP1) in liver injury

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dc.contributor.advisorHengstler, Jan G.
dc.contributor.authorGonzález Leiva, Daniela Fernanda
dc.contributor.refereeWatzl, Carsten
dc.date.accepted2021-01-26
dc.date.accessioned2021-02-18T14:23:21Z
dc.date.available2021-02-18T14:23:21Z
dc.date.issued2020
dc.description.abstractLiver diseases are a global burden and a better understanding of factors controlling disease progression is required. In the last decade, much progress has been achieved in understanding the relevance of the extracellular matrix. Alterations in this dynamic structure can either facilitate or impair the repair of damaged liver tissue. Therefore, matricellular proteins of the CCN family, have emerged as new targets in liver pathophysiology. These highly conserved secreted proteins specifically interact with and signal through various extracellular partners, like integrins, which enable them to play crucial roles in various processes including development, wound healing and diseases such as cancer and fibrosis. We have discovered that WISP1 (Wnt1-inducible signaling pathway protein-1) also named CCN4, is induced upon CCl4-induced liver damage and may play an important role in the remodeling process of the extracellular matrix. Therefore, the aims were to identify the cell type that produces WISP1, to study its influence in cell migration and to use WISP1 KO mice to understand its role in the pathogenesis of liver fibrosis. Isolation of individual liver cell types and quantification of WISP1 expression and secretion showed a higher mRNA expression and TGF-β-induced secretion of WISP1 in non-parenchymal cells, especially in stellate cells compared to hepatocytes. Furthermore, WISP1 facilitated the migration of isolated mouse hepatic stellate cells through collagen lattices, suggesting the interaction of WISP1 with one of the main components of the extracellular matrix and affecting its architecture. Additionally, gene expression analysis and Sirius Red staining showed differences in the development of CCl4-induced fibrosis between WISP1 wild type and knockout mice. Upregulation of collagen type I and α-SMA is reduced in WISP1 KO mice and less collagen deposition is also observed. In conclusion, WISP1 is mainly expressed and secreted by stellate cells which may influence their migration upon liver injury and consequently, ameliorating the degree of liver fibrosis.en
dc.identifier.urihttp://hdl.handle.net/2003/40035
dc.identifier.urihttp://dx.doi.org/10.17877/DE290R-21916
dc.language.isoende
dc.subjectWISP1en
dc.subjectLiveren
dc.subjectMigrationen
dc.subjectHSCen
dc.subjectECMen
dc.subjectCollagenen
dc.subjectCCl4en
dc.subject.ddc540
dc.subject.ddc570
dc.subject.rswkLeberde
dc.subject.rswkLebererkrankungde
dc.titleRole of WNT1-inducible signaling pathway protein-1 (WISP1) in liver injuryen
dc.typeTextde
dc.type.publicationtypedoctoralThesisde
dcterms.accessRightsopen access
eldorado.secondarypublicationfalsede

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Lehrstuhl für Umweltchemie und Analytische Chemie