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Hypoxia-pretreatment as a possible approach to stimulate wound healing potentials of dermal fibroblasts in treatment of chronic skin ulcersстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: EV Solovieva, KA Darienko, AA Panteleyev
- Журнал: Journal of Investigative Dermatology
- Том: 139
- Год издания: 2019
- Издательство: Blackwell Publishing Inc.
- Местоположение издательства: United Kingdom
- Аннотация: In non-healing diabetic ulcers (diabetic foot) auto-transplantation (a common treatment approach) is not effective due to impaired fibroblast functionality and shifts in synthesis of ECM proteins (COL1, COL3, FN) and certain growth factors. It was shown that HIF1 (hypoxia-induced factor) is a key regulator of ECM remodeling by fibroblasts through control of collagen prolyl hydroxylase (P4HA1, P4HA2 e both required for collagen deposition) and lysylhydroxylase (PLOD2 emodulates collagen fibers strength) expression. Therefore, the use of hypoxia-stimulated fibroblasts (sFbs) may represent a reasonable treatment alternative in the maintenance of chronic diabetic wounds. Here, we evaluated the expression levels of wound healing-related genes and proteins in sFbs after 24h, 48h and 72h exposure to 1% O2. After a short-term (24/48h) exposure to hypoxia, sFbs exhibited a marked increase in expression of a number of genes as compared to 21% O2 culture: Hif1a e7.4 and 16.9 fold respectively; Vegf1a e21/60; Egln1 e9/9; Egln2 e6.5/5; Egln3 e53/110; COL1 e2.4/3; Fn e 3.3/1.7; P4HAa1 - 5.8/7.8; P4ha2 e 6.6/8.5; and Plod2 - 9/25 fold. In contrast, with a longer exposure to hypoxia (72h), activation was significantly diminished (Hif1a e 2 fold; Vegf1a e6; Egln3 e2.4) or completely abrogated (Egln1, Egln2, COL1, Fn, P4ha1, P4ha2, and Plod2). Importantly, at protein level, we observed only COLI (2 fold) stimulation by hypoxia. The stimulation of COLIII and Fn synthesis in sFb was detected only after a 6-18h period of their re-oxygenation. Based on our results, we propose that short-term stimulation of dermal fibroblasts (for example, immobilized on a biopolymer scaffold) by hypoxia could be beneficial for chronic diabetic wound treatment.
- Добавил в систему: Соловьева Елена Викторовна