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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.

Authors

Sarah Baghestani

Ada Pajari

M. Bishr Omary

Diana M. Toivola



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 β-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 β-cells in wild-type mice and along the lateral membrane, in addition to forming a fine cytoplasmic network. In K8‒/‒ β-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 β-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
Electronic ISSN 1422-0067
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
Related Public URLs https://europepmc.org/articles/PMC8346022
PMID 34360548

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