beta multifunctionality
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INTRODUCTION: One route of translating the information encoded in the glycan chains of cellular glycoconjugates into physiological effects is via receptor (lectin) binding. A family of endogenous lectins, sharing folding, a distinct sequence signature and affinity for β-galactosides (thus termed galectins), does so effectively in a context-dependent manner. AREAS COVERED: An overview is given on the multifunctional nature of galectins, with emphasis on galectin-1. The broad range of functions includes vital processes such as adhesion via glycan bridging, glycoconjugate transport or triggering signaling relevant, for example, for growth regulation. Besides distinct glycoconjugates, this lectin can also interact with certain proteins so that it can target counterreceptors at all sites of location, that is, in the cytoplasm and/or nucleus, at both sides of the membrane or extracellularly. Approaches to strategically exploit galectin activities with therapeutic intentions are outlined. EXPERT OPINION: The wide versatility of sugar coding and the multifunctionality of galectin-1 explain why considering to turn the protein into a therapeutic target is an ambitious aim. Natural pathways shaped by physiologic master regulators (e.g., the tumor suppressor p16(INK4a)) are suggested to teach inspiring lessons as to how the lectin might be recruited to clinical service.
- MeSH
- biologický transport účinky léků MeSH
- buněčná adheze účinky léků MeSH
- cílená molekulární terapie MeSH
- galektin 1 antagonisté a inhibitory metabolismus MeSH
- galektiny antagonisté a inhibitory metabolismus MeSH
- glykokonjugáty metabolismus MeSH
- lidé MeSH
- nádorové proteiny antagonisté a inhibitory metabolismus MeSH
- nádory farmakoterapie prevence a kontrola MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky farmakologie terapeutické užití MeSH
- racionální návrh léčiv * MeSH
- signální transdukce účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Members of the galectin family of endogenous lectins are potent adhesion/growth-regulatory effectors. Their multifunctionality opens possibilities for their use in bioapplications. We studied whether human galectins induce the conversion of human dermal fibroblasts into myofibroblasts (MFBs) and the production of a bioactive extracellular matrix scaffold is suitable for cell culture. Testing a panel of galectins of all three subgroups, including natural and engineered variants, we detected activity for the proto-type galectin-1 and galectin-7, the chimera-type galectin-3 and the tandem-repeat-type galectin-4. The activity of galectin-1 required the integrity of the carbohydrate recognition domain. It was independent of the presence of TGF-β1, but it yielded an additive effect. The resulting MFBs, relevant, for example, for tumor progression, generated a matrix scaffold rich in fibronectin and galectin-1 that supported keratinocyte culture without feeder cells. Of note, keratinocytes cultured on this substratum presented a stem-like cell phenotype with small size and keratin-19 expression. In vivo in rats, galectin-1 had a positive effect on skin wound closure 21 days after surgery. In conclusion, we describe the differential potential of certain human galectins to induce the conversion of dermal fibroblasts into MFBs and the generation of a bioactive cell culture substratum.
- MeSH
- extracelulární matrix metabolismus MeSH
- fibroblasty metabolismus MeSH
- galektin 1 metabolismus MeSH
- galektin 3 metabolismus MeSH
- galektin 4 metabolismus MeSH
- galektiny metabolismus MeSH
- hojení ran MeSH
- keratin-19 metabolismus MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- myofibroblasty metabolismus MeSH
- tkáňové inženýrství metody MeSH
- transformující růstový faktor beta1 metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH