Characterizing the role of WISP1 in liver pathophysiology
Gastroenterology
Final Report Abstract
The mechanisms underlying the remarkable capacity of the liver to regenerate are still not completely understood. Particularly, the cross talk between cytokines and cellular components of the process are of outmost importance because they represent potential avenues for diagnostics and therapeutics. Our investigations indicate that WISP1 is a direct target of TGF-β, a critical cytokine in wound healing processes. Additionally, WISP1 is strongly expressed and secreted by all liver cells, especially by hepatic stellate cells upon TGF-β stimulation. Furthermore, WISP1 facilitates 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. 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 a tendency towards reduced length of fibrotic streets was observed. In conclusion, WISP1 is mainly expressed and secreted by stellate cells which may influence their migration remodeling collagen upon liver injury. An important drawback in our project was presented in the middle of the project period. The reproducibility of the WISP1 KO phenotype after acute liver damage was difficult to achieve and still needs some clarification with further experiments. Nevertheless, we found strong evidence of WISP1 influence in the architecture of collagen and a role in the pathogenesis of liver diseases such as liver fibrosis, which will be additionally confirmed with further experiments.
Publications
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Ebmeyer, J.; Rasinger, J. D.; Hengstler, J. G.; Schaudien, D.; Creutzenberg, O.; Lampen, A.; Braeuning, A.; Hessel- Pras, S.
(See online at https://doi.org/10.1007/s00204-020-02779-2) - Inflammationassociated suppression of metabolic gene networks in acute and chronic liver disease Arch. Toxicol. 94: 205-217 (2020)
Campos, G.; Ghallab, A.; Pütter, L.; Edlund, K.; Cadenas, C.; Marchan, R.; Hengstler, J. G.; Godoy, P.
(See online at https://doi.org/10.1007/s00204-019-02630-3) - Towards improved hepatocyte cultures: Progress and limitatios. Food Chem. Toxicol. 138: article no. 111188 (2020)
Ruoß, M.; Vosough, M.; Königsrainer, A.; Nadalin, S.; Wagner, S.; Sajadian, S.; Hengstler, J. G.; Nussler, A. K.
(See online at https://doi.org/10.1016/j.fct.2020.111188)
