Cathepsin B is essential for regeneration of scratch-wounded normal human epidermal keratinocytes

Büth, Heiko; Buttigieg, Pier Luigi; Ostafe, Raluca; Rehders, Maren; Dannenmann, Stefanie R.; Schaschke, Norbert; Stark, Hans Jürgen; Boukamp, Petra; Brix, Klaudia

doi:10.1016/j.ejcb.2007.03.009

Cited by 57 publications

(44 citation statements)

References 47 publications

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“…Undoubtedly, cathepsin K is one of the cysteine peptidases with such functions in cancer [54,[74][75][76][77]. However, ECM degradation besides type I collagen processing in bone turnover has also been shown to occur in physiology for tissue remodelling during wound healing of the skin or the gastro-intestinal tract and to be mediated by a number of different cysteine cathepsins, namely cathepsins B, D and L [22,29,32,78].…”

Section: Bone As a Th Target Tissuementioning

confidence: 98%

Thyroid Cathepsin K: Roles in Physiology and Thyroid Disease

Dauth

Arampatzidou

Rehders

et al. 2011

Clinic Rev Bone Miner Metab

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The human genome encodes 11 cysteine cathepsins belonging to the papain-like family of cysteine peptidases that are known predominantly as endo-lysosomal enzymes. However, it is now understood that the functions and activities of cysteine cathepsins are not limited to endo-lysosomal compartments, as they are also active in the peri-and extracellular space. The thyroid gland is an endocrine organ where such intra-and extracellular proteolytic activities are required to solubilize the prohormone thyroglobulin from its luminal, covalently cross-linked storage forms for subsequent processing into smaller protein fragments and thyroid hormone liberation. Cathepsin K has been identified as one of the cysteine cathepsins with a crucial role in thyroglobulin processing. However, cathepsin K has mainly been a key focus of attention in the last few years because of its high expression in osteoclasts and due to its essential role as collagenase and elastase important for bone remodelling. Besides its remarkable function as an endopeptidase acting on highmolecular mass, covalently cross-linked extracellular substrates such as type I collagen, elastin or thyroglobulin, cathepsin K is also one of the very few proteolytic enzymes that is able to directly liberate thyroxine from thyroglobulin fragments by exopeptidase action. Thus, thyroid cathepsin K is now accepted as a cysteine peptidase with a vital role in liberation of thyroid hormones, which in turn are essential for homoeostasis by triggering a number of important biological processes, ranging from growth and brain development in young vertebrates to tissue remodelling events during morphogenesis or wound healing, as well as control of metabolic pathways and thermoregulation in adults. This review focuses on thyroid cathepsin K and will discuss how localization and trafficking within thyroid epithelial cells explain its thyroid-specific functions. The effects of targeted cathepsin K gene ablation will be summarized from the perspective of the thyroid gland, and we will propose potential consequences of short-and long-term inhibition of thyroid cathepsin K activity for the main thyroid hormone target tissues, namely bone, cardiovascular and immune systems, intestine, and the central nervous system, in addition to the thyroid gland itself.

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Section: Bone As a Th Target Tissuementioning

confidence: 98%

Thyroid Cathepsin K: Roles in Physiology and Thyroid Disease

Dauth

Arampatzidou

Rehders

et al. 2011

Clinic Rev Bone Miner Metab

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“…In addition, procathepsin X is well known to interact with integrins, to regulate other cellular processes such as cell-cell adhesion and lymphocyte activation but in a non-proteolytic fashion (Lechner et al 2006;Lines et al 2012). An example where cysteine cathepsins cleave extracellular matrix components like collagen IV under physiological conditions at neutral pH is seen by epidermal keratinocytes which secrete cathepsin B upon mechanical scratch wounding for ECM degradation to ease keratinocyte migration for wound healing and tissue regeneration (Buth et al 2007). Another example is provided by investigations on the gastro-intestinal tract, where cysteine cathepsins resume functions in the extracellular space of the mucosa during tissue regeneration from mechanical trauma, or where cysteine cathepsins are active even at the gut lumen-exposed apical side of the mucosal wall (Arampatzidou et al 2012;Mayer et al 2009;Tamhane et al 2014;Vreemann et al 2009).…”

Section: Endo-lysosomal Cysteine Peptidases: Myths and Common Questionsmentioning

confidence: 99%

Proteolysis mediated by cysteine cathepsins and legumain—recent advances and cell biological challenges

et al. 2014

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Proteases play essential roles in protein degradation, protein processing, and extracellular matrix remodeling in all cell types and tissues. They are also involved in protein turnover for maintenance of homeostasis and protein activation or inactivation for cell signaling. Proteases range in function and specificity, with some performing distinct substrate cleavages, while others accomplish proteolysis of a wide range of substrates. As such, different cell types use specialized molecular mechanisms to regulate the localization of proteases and their function within the compartments to which they are destined. Here, we focus on the cysteine family of cathepsin proteases and legumain, which act predominately within the endo-lysosomal pathway. In particular, recent knowledge on cysteine cathepsins and their primary regulator legumain is scrutinized in terms of their trafficking to endo-lysosomal compartments and other less recognized cellular locations. We further explore the mechanisms that regulate these processes and point to pathological cases which arise from detours taken by these proteases. Moreover, the emerging biological roles of specific forms and variants of cysteine cathepsins and legumain are discussed. These may be decisive, pathogenic, or even deadly when localizing to unusual cellular compartments in their enzymatically active form, because they may exert unexpected effects by alternative substrate cleavage. Hence, we propose future perspectives for addressing the actions of cysteine cathepsins and legumain as well as their specific forms and variants. The increasing knowledge in non-canonical aspects of cysteine cathepsin- and legumain-mediated proteolysis may prove valuable for developing new strategies to utilize these versatile proteases in therapeutic approaches.

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“…The method allows the direct measurement of cell migration and layer regeneration. Using the scratch apparatus described by Büth et al [20] , the scratches can be applied with high precision and in reproducible fashion. However, monolayer cultures lack the three-dimensional environment of intact tissue.…”

Section: Trends In Biocompatibility Studymentioning

confidence: 99%

“…Both degradation and reformation of the matrix are functions performed by dermal fibroblasts and epidermal keratinocytes. The mechanical scratch wounding of confluent monolayers serves as a model to study cell migration at the wound margins [20] . The method allows the direct measurement of cell migration and layer regeneration.…”

Section: Trends In Biocompatibility Studymentioning

confidence: 99%

Evaluation of Biocompatibility and Cytotoxicity Using Keratinocyte and Fibroblast Cultures

Wiegand¹,

Hipler²

2009

Skin Pharmacol Physiol

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Determination of biocompatibility and cytotoxicity is part of the initial evaluation of medical devices stipulated by ISO standards on biological evaluation of medical devices. Cell culture systems for testing biological reactions to drugs, biomaterials or treatment techniques used in various disciplines have been gaining importance. A wide variety of cell lines are commonly used: cultured fibroblasts from human skin, buccal mucosa, periodontal membrane or embryonic lung; epithelial and HeLa cells; cultures of human keratinocytes and HaCaT cells; different murine cell lines (C3H-L, Balb/c 3T3, L929 and others) as well as murine cells cultured from liver and spleen; T lymphocytes from lymph nodes and macrophages obtained by lavage. All these cells are suitable for the use in biocompatibility tests. Nevertheless, the general opinion is that cytotoxicity tests in vitro will be more convincing when performed with cells that are homologous with the human tissue concerned. In accordance, appropriate cell lines for the use in cytotoxicity and tolerance tests concerning the skin would be human dermal fibroblasts and human epidermal keratinocytes, as they take an active part in the immune response, inflammatory processes and wound healing.

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Cathepsin B is essential for regeneration of scratch-wounded normal human epidermal keratinocytes

Cited by 57 publications

References 47 publications

Thyroid Cathepsin K: Roles in Physiology and Thyroid Disease

Thyroid Cathepsin K: Roles in Physiology and Thyroid Disease

Proteolysis mediated by cysteine cathepsins and legumain—recent advances and cell biological challenges

Evaluation of Biocompatibility and Cytotoxicity Using Keratinocyte and Fibroblast Cultures

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