Effect of Tff3 Deficiency and ER Stress in the Liver

• Main Authors: Kate Šešelja, Iva Bazina, Jessica Welss, Martin Schicht, Friedrich Paulsen, Nikola Bijelić, Edi Rođak, Anita Horvatić, Andrea Gelemanović, Martina Mihalj, Mirela Baus Lončar
• Format: Article
• Language: English
• Published: MDPI AG 2019-09-01
• Series: International Journal of Molecular Sciences
• Subjects: ER stress; trefoil peptide 3; liver; tunicamycin; proinflammatory cytokines
• Online Access: https://www.mdpi.com/1422-0067/20/18/4389

Endoplasmic reticulum (ER) stress, a cellular condition caused by the accumulation of unfolded proteins inside the ER, has been recognized as a major pathological mechanism in a variety of conditions, including cancer, metabolic and neurodegenerative diseases. Trefoil factor family (TFFs) peptides are present in different epithelial organs, blood supply, neural tissues, as well as in the liver, and their deficiency has been linked to the ER function. Complete ablation of <i>Tff3</i> expression is observed in steatosis, and as the most prominent change in the early phase of diabetes in multigenic mouse models of diabesity. To elucidate the role of <i>Tff3</i> deficiency on different pathologically relevant pathways, we have developed a new congenic mouse model <i>Tff3^{&#8722;/&#8722;}</i>/C57BL6/N from a mixed background strain (C57BL6/N /SV129) by using a speed congenics approach. Acute ER stress was evoked by tunicamycin treatment, and mice were sacrificed after 24 h. Afterwards the effect of <i>Tff3</i> deficiency was evaluated with regard to the expression of relevant oxidative and ER stress genes, relevant proinflammatory cytokines/chemokines, and the global protein content. The most dramatic change was noticed at the level of inflammation-related genes, while markers for unfolded protein response were not significantly affected. Ultrastructural analysis confirmed that the size of lipid vacuoles was affected as well. Since the liver acts as an important metabolic and immunological organ, the influence of <i>Tff3</i> deficiency and physiological function possibly reflects on the whole organism.