Roles of keratins in intestinal health and disease

.................................................................................................................. 6 LIST OF ORIGINAL PUBLICATIONS (THESIS) .................................................. 7 LIST OF ORIGINAL PUBLICATIONS (NOT IN THESIS) ................................... 8 ABBREVIATIONS ........................................................................................................ 9 1. INTRODUCTION .................................................................................................. 11 2. REVIEW OF THE LITERATURE ...................................................................... 13 2.1. Overview of the intermediate filaments ............................................................ 13 2.1.1. Classification of intermediate filaments ................................................. 13 2.1.2. Main IF functions and IF-pathies ............................................................ 14 2.2. Keratins ............................................................................................................. 15 2.2.1. Keratin nomenclature and structure ........................................................ 15 2.2.2. Simple Epithelial Keratins (SEK) with unique tissue and cell specific expression ............................................................................................... 17 2.2.3. Keratin Regulation .................................................................................. 20 2.2.3.1. Keratins and PTMs .................................................................. 20 2.2.3.2. Keratin binding proteins .......................................................... 22 2.2.4. Functions of SEKs .................................................................................. 22 2.2.4.1. Scaffolding and cytoprotective functions of SEK ................... 23 2.2.4.2. Protein targeting functions of SEK .......................................... 24 2.2.5. Human diseases linked with SEK IFs ..................................................... 25 2.2.6. The role of SEKs in the small intestine and colon .................................. 27 2.3. Epithelial ion transport ...................................................................................... 31 2.3.1. Ion transporters ....................................................................................... 31 2.3.2. Sodium transporters ................................................................................ 31 2.3.2.1. ENaC ....................................................................................... 32 2.3.2.2. NHE ......................................................................................... 32 2.3.3. Chloride transporters ............................................................................... 33 2.3.3.1. AE1/2 ....................................................................................... 33 2.3.3.2. PAT-1 ...................................................................................... 33 2.3.3.3. DRA ......................................................................................... 34 2.3.3.4. CFTR ....................................................................................... 36 2.3.4. Keratins in intestinal ion transport .......................................................... 36 2.4. Inflammatory Bowel Disease (IBD) ................................................................. 36 2.4.1. IBD diagnostics ....................................................................................... 38 2.4.2. Reactive oxygen and nitrogen species (RONS) in IBD .......................... 38 2.4.3. Measurement of RONS and in vivo imaging of murine colitis ............... 39