Roles of cysteine cathepsins in intestinal homeostasis

  • Cysteine cathepsins are endo-lysosomal proteases expressed in a variety of cells and tissues, including the gastrointestinal tract. Trafficking and localization studies have changed the classical view of cysteine cathepsins as enzymes acting only intracellularly and now it is well established that these proteases can also be secreted and exert extracellular functions. For example, extracellular cathepsin K has been recently indentified as an intestinal antibacterial factor with anti-inflammatory potential. Our studies on cathepsin K-deficient mice demonstrated that absence of cathepsin K is accompanied by elevated levels of other cysteine cathepsins, namely cathepsins B, L, and X. In addition, cathepsin K-deficient mice exhibited higher protein levels of collagen IV, an observation also shown for cathepsin B- and cathepsin L-deficient mice. These findings made us propose a role of cysteine cathepsins in ECM remodeling through both direct and indirect effects. Moreover, this study revealed that cathepsin K is important for the intestinal barrier function, since absence of this protease resulted in impaired distribution and expression of intercellular junction proteins. An important and very interesting observation was that cathepsin-deficiency affects each part of the gastrointestinal tract differently. For the first time each part of the small and large intestine was analyzed separately and our observations revealed that the proteolytic profile is unique and characteristic for each intestinal part. Interestingly, elevated levels of cathepsin X were found only in the duodenum and colon of cathepsin B-deficient mice when compared to wild type controls, while no alterations were observed in the case of jejunum and ileum. Hence, the conditions required for compensatory tasks of cathepsin X might be present only in specific parts of the gastrointestinal tract. Overall, this study demonstrates the key role of cysteine cathepsins in intestinal homeostasis and highlights the necessity to investigate each part of the gastrointestinal tract independently and not as an entity.

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Publishing Institution:IRC-Library, Information Resource Center der Jacobs University Bremen
Granting Institution:Jacobs Univ.
Author:Maria Arampatzidou
Referee:Klaudia Brix, Georgi Muskhelishvili, Matthias Ullrich, Margarete Heck
Advisor:Klaudia Brix
Persistent Identifier (URN):urn:nbn:de:101:1-2013052812556
Document Type:PhD Thesis
Language:English
Date of Successful Oral Defense:2012/05/11
Year of Completion:2012
Date of First Publication:2012/05/31
PhD Degree:Cell Biology
School:SES School of Engineering and Science
Library of Congress Classification:Q Science / QP Physiology / QP501-801 Animal biochemistry / QP525-801 Special substances / QP550-801 Organic substances / QP551-619 Proteins, amino acids, etc. / QP601-619 Enzymes / QP608-609 Hydrolases / QP609.A-Z Special, A-Z / QP609.C35 Cathepsin
Call No:Thesis 2012/9

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