Publication Database

RNA Sequenceing, Gene Expression Analysis, and immunohistochemical studies in dogs with chronic hepatitis and hepatic fibrosis (2018)

Art

Hochschulschrift

Autor

Eulenberg, Vera Marianne (WE 20)

Quelle

Berlin: Mensch und Buch Verlag Berlin, 2018 — 144 Seiten

ISBN: 978-3-86387-886-3

Sprache

Englisch

Verweise

URL (Volltext): https://refubium.fu-berlin.de/handle/fub188/27470

Kontakt

Klein- und Heimtierklinik

Oertzenweg 19 b
14163 Berlin
+49 30 838 62422
kleintierklinik@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Chronic hepatitis is a well-recognized cause for hepatic fibrosis in dogs. For the majority of chronic hepatitis cases an etiology cannot be determined and the pathophysiology of chronic hepatitis and hepatic fibrosis is still not fully understood. Evaluation of gene expression can provide insight into disease mechanisms and lead to the identification of candidate biomarkers. The aim of the RNA sequencing study was to identify differential gene expression in dogs with chronic hepatitis compared to healthy control dogs. Additionally, tissue expression of selected markers was investigated by immunohistochemistry. The first part of this study analyzed the transcriptome of liver samples of dogs with chronic hepatitis and fibrosis compared to healthy dogs. Six-hundred-and-fifty-one genes were significantly differentially expressed in dogs with chronic hepatitis. Pathway analysis revealed a connection to pathways involved in hepatic fibrosis: genes for growth factors (e.g., CTGF, PDGFD), chemokines and chemokine receptors (e.g., CCL2, CCL5, CXCL10, CCR5, CXCR3), matrix collagens (e.g., Col1A1, Col3A1), and genes for ECM remodeling (e.g., TIMP-1, MATN3, ADAMDEC1, CHI3L1, MMP9, MMP2) are upregulated in dogs with hepatic fibrosis. These genes also play important roles in the pathophysiology of hepatic fibrosis in humans. The second part of the study investigated the tissue distribution and expression of cytoglobin, tissue inhibitor of metalloproteinase 1, proliferation marker Ki67, and alpha- smooth muscle actin with immunohistochemistry. Expression was evaluated in association with the fibrotic stage. Neither cytoglobin nor tissue inhibitor of metalloproteinase 1 were shown to be specific markers for hepatic stellate cells or were able to distinguish between quiescent and activated hepatic stellate cells. However, Ki67 and alpha-smooth muscle actin were differentially expressed between dogs with different stages of hepatic fibrosis.