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Immortalized kerati...
Immortalized keratinocytes derived from patients with epidermolytic ichthyosis reproduce the disease phenotype : A useful in vitro model for testing new treatments
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- Chamcheu, Jean Christopher (författare)
- Uppsala universitet,Dermatologi och venereologi,Dermatologi och venereologi, Dermatology and Venereology
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- Pihl-Lundin, Inger (författare)
- Uppsala universitet,Dermatologi och venereologi,Dermatology and Venereology
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- Eteti Mouyobo, Cedrique (författare)
- Uppsala universitet,Dermatologi och venereologi
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- Gester, Therese (författare)
- Uppsala universitet,Dermatologi och venereologi
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- Virtanen, Marie (författare)
- Uppsala universitet,Dermatologi och venereologi,Dermatology and Venereology
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- Moustakas, Aristidis (författare)
- Uppsala universitet,Ludwiginstitutet för cancerforskning,Institutionen för medicinsk biokemi och mikrobiologi
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- Navsaria, Harshad (författare)
- Centre for Cutaneous Research, Queen Mary’s School of Medicine and Dentistry, London E1 2AT, U.K.,ICMS, Centre for Cutaneous Research
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- Vahlquist, Anders (författare)
- Uppsala universitet,Dermatologi och venereologi,Dermatology and Venereology
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- Törmä, Hans (författare)
- Uppsala universitet,Dermatologi och venereologi,Dermatology and Venereology
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(creator_code:org_t)
- 2011-01-28
- 2011
- Engelska.
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Ingår i: British Journal of Dermatology. - : British Association of Dermatologists. - 0007-0963 .- 1365-2133. ; 164:2, s. 263-272
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: Epidermolytic ichthyosis (EI) is a skin fragility disorder caused by mutations in genes encoding suprabasal keratins 1 and 10. While the aetiology of EI is known, model systems are needed for pathophysiological studies and development of novel therapies. Objectives To generate immortalized keratinocyte lines from patients with EI for studies of EI cell pathology and the effects of chemical chaperones as putative therapies. Methods We derived keratinocytes from three patients with EI and one healthy control and established immortalized keratinocytes using human papillomavirus 16-E6/E7. Growth and differentiation characteristics, ability to regenerate organotypic epidermis, keratin expression, formation of cytoskeletal aggregates, and responses to heat shock and chemical chaperones were assessed. Results The cell lines EH11 (K1-p.Val176-Lys197del), EH21 (K10-p.156Arg>Gly), EH31 (K10-p.Leu161-Asp162del) and NKc21 (wild-type) currently exceed 160 population doublings and differentiate when exposed to calcium. At resting state, keratin aggregates were detected in 9% of calcium-differentiated EH31 cells, but not in any other cell line. Heat stress further increased this proportion to 30% and also induced aggregates in 3% of EH11 cultures. Treatment with trimethylamine N-oxide and 4-phenylbutyrate (4-PBA) reduced the fraction of aggregate-containing cells and affected the mRNA expression of keratins 1 and 10 while 4-PBA also modified heat shock protein 70 (HSP70) expression. Furthermore, in situ proximity ligation assay suggested a colocalization between HSP70 and keratins 1 and 10. Reconstituted epidermis from EI cells cornified but EH21 and EH31 cells produced suprabasal cytolysis, closely resembling the in vivo phenotype. Conclusions These immortalized cell lines represent a useful model for studying EI biology and novel therapies.
Nyckelord
- MEDICINE
- MEDICIN
- Dermatology and Venerology
- Dermatologi och venereologi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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