Role of carbonic anhydrases in skin wound healing
Autor: | Hannele Uusitalo-Järvinen, Abdul Waheed, Silvia Pastorekova, Maria Vähätupa, Seppo Parkkila, William S. Sly, Peiwen Pan, Marleena Aaltonen, Pirkka Kaipiainen, Harlan Barker, Stuart Prince, Ulrike May, Tero A. H. Järvinen |
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Přispěvatelé: | Lääketieteen ja biotieteiden tiedekunta - Faculty of Medicine and Life Sciences, University of Tampere |
Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
Male
0301 basic medicine Gene isoform Pathology medicine.medical_specialty Angiogenesis Bicarbonate Clinical Biochemistry Biology Biochemistry Biokemia solu- ja molekyylibiologia - Biochemistry cell and molecular biology Mice 03 medical and health sciences chemistry.chemical_compound Re-Epithelialization medicine Animals Humans Protein Isoforms Molecular Biology Carbonic Anhydrases Skin chemistry.chemical_classification Mice Inbred BALB C integumentary system Cell migration Hypoxia (medical) Cell Hypoxia Cell biology 030104 developmental biology Enzyme chemistry Molecular Medicine Original Article Stem cell medicine.symptom Wound healing |
Zdroj: | Experimental & Molecular Medicine |
Popis: | Skin wound closure occurs when keratinocytes migrate from the edge of the wound and re-epithelialize the epidermis. Their migration takes place primarily before any vascularization is established, that is, under hypoxia, but relatively little is known regarding the factors that stimulate this migration. Hypoxia and an acidic environment are well-established stimuli for cancer cell migration. The carbonic anhydrases (CAs) contribute to tumor cell migration by generating an acidic environment through the conversion of carbon dioxide to bicarbonate and a proton. On this basis, we explored the possible role of CAs in tissue regeneration using mouse skin wound models. We show that the expression of mRNAs encoding CA isoforms IV and IX are increased (~25 × and 4 ×, respectively) during the wound hypoxic period (days 2–5) and that cells expressing CAs form a band-like structure beneath the migrating epidermis. RNA-Seq analysis suggested that the CA IV-specific signal in the wound is mainly derived from neutrophils. Due to the high level of induction of CA IV in the wound, we treated skin wounds locally with recombinant human CA IV enzyme. Recombinant CA IV significantly accelerated wound re-epithelialization. Thus, CA IV could contribute to wound healing by providing an acidic environment in which the migrating epidermis and neutrophils can survive and may offer novel opportunities to accelerate wound healing under compromised conditions. |
Databáze: | OpenAIRE |
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