Keratin 7 Is a Constituent of the Keratin Network in Mouse Pancreatic Islets and Is Upregulated in Experimental Diabetes

Alam, Catharina M.; Baghestani, Sarah; Pajari, Ada; Omary, M. Bishr; Toivola, Diana M.

Abstract

Keratin (K) 7 is an intermediate filament protein expressed in ducts and glands of simple epithelial organs and in urothelial tissues. In the pancreas, K7 is expressed in exocrine ducts, and apico-laterally in acinar cells. Here, we report K7 expression with K8 and K18 in the endocrine islets of Langerhans in mice. K7 filament formation in islet and MIN6 ?-cells is dependent on the presence and levels of K18. K18-knockout (K18?/?) mice have undetectable islet K7 and K8 proteins, while K7 and K18 are downregulated in K8?/? islets. K7, akin to F-actin, is concentrated at the apical vertex of ?-cells in wild-type mice and along the lateral membrane, in addition to forming a fine cytoplasmic network. In K8?/? ?-cells, apical K7 remains, but lateral keratin bundles are displaced and cytoplasmic filaments are scarce. Islet K7, rather than K8, is increased in K18 over-expressing mice and the K18-R90C mutation disrupts K7 filaments in mouse ?-cells and in MIN6 cells. Notably, islet K7 filament networks significantly increase and expand in the perinuclear regions when examined in the streptozotocin diabetes model. Hence, K7 represents a significant component of the murine islet keratin network and becomes markedly upregulated during experimental diabetes.

Citation

Alam, C. M., Baghestani, S., Pajari, A., Omary, M. B., & Toivola, D. M. (2021). Keratin 7 Is a Constituent of the Keratin Network in Mouse Pancreatic Islets and Is Upregulated in Experimental Diabetes. International Journal of Molecular Sciences, 22(15), Article 7784. https://doi.org/10.3390/ijms22157784

• Journal Article Type: Article
• Acceptance Date: Jul 13, 2021
• Online Publication Date: Jul 21, 2021
• Publication Date: 2021
• Deposit Date: May 6, 2022
• Publicly Available Date: May 6, 2022
• Journal: International Journal of Molecular Sciences
• Print ISSN: 1661-6596
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 22
• Issue: 15
• Article Number: 7784
• DOI: https://doi.org/10.3390/ijms22157784
• Keywords: beta-cell; islet; keratin; Krt7; diabetes; stress; polarity; MIN6
• Public URL: http://researchrepository.napier.ac.uk/Output/2869028