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

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

doi:10.3390/ijms22157784

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.

Highlights

Keratin (K) 7 is a type II intermediate filament (IF) protein expressed primarily in simple-type epithelia of glandular and ductal cells, but it is expressed in stratified and transitional epithelia of urothelial and mesothelial tissues [1,2]
K7 and K19 expression is limited to the ducts and the acinar apico-lateral domain in mouse pancreas, and in some human and rodent studies, K7 expression has been described exclusively in the exocrine pancreatic ducts, where it pairs with the type I K19 [3,5]
Immunostaining of wild-type mouse pancreas sections (Figure 1A) and immunoblot analysis of isolated islets (Figure 1B) showed that, in addition to K8 and K18, pancreatic islets in mice express substantial amounts of K7 which co-localizes with K8 and K18 (Figure 1A)

Summary

Introduction

Keratin (K) 7 is a type II intermediate filament (IF) protein expressed primarily in simple-type epithelia of glandular and ductal cells, but it is expressed in stratified and transitional epithelia of urothelial and mesothelial tissues [1,2]. K7 is widely expressed in the ductal cells of the liver, kidney, and pancreas, and in subpopulations of cells in gastrointestinal and lung epithelia [3]. K8 and K18 have been described as the major keratins in exocrine acinar cells, as well as endocrine islets [4,5,6,7]. K7 and K19 expression is limited to the ducts and the acinar apico-lateral domain in mouse pancreas, and in some human and rodent studies, K7 expression has been described exclusively in the exocrine pancreatic ducts, where it pairs with the type I K19 [3,5]. K7 is generally considered a ductal marker in the pancreas and liver in humans and experimental mammalian models, with some reports describing its presence in pancreatic islets

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