Title (srp)

Улога локалне нише епидермалних матичних ћелија у настанку и развоју хроничних венских улкуса

Author

Stojadinović, Olivera, 1972-

Contributor

Tomić-Canić, Marjana, 1958-
Arsenijević, Nebojša, 1963-
Vojvodić, Danilo, 1976-
Radosavljević, Gordana, 1979-
Milovanović, Marija

Description (srp)

Epidermis kože čoveka je višeslojni pločasti keratinizovan epitel koji seneprekidno obnavlja od strane epidermalnih matičnih ćelija. Ove ćelije se nalaze ubazalnom sloju kože i folikulu dlake i neprekidno obezbeđuju održavanje homeostazekože. Epidermalne matične ćelije takođe učestvuju i u zarastanju rana. Poznato je da sukod pacijenata koji boluju od hroničnih venskih ulcera, keratinociti na obodimanavedenih promena izmenjeni i nisu u mogućnosti da obezbede normalno zarastanje rana.Ovaj rad predstavlja prospektivnu kliničku studiju koja je obuhvatila 11 pacijenata sahroničnim venskim ulceracijama u okviru koje je, analizom transkripcionih profilana uzorcima humanog tkiva, pokazano da postoje promene u ekspresiji specifičnih gena(GATA3, BMPR1, ID2, ID4, LRIG1 i K15) koji regulišu održavanje matičnih ćelija injihovu diferencijaciju. Smanjena ekspresija ovih gena ukazuje na osiromašenupopulaciju epidermalnih matičnih ćelija.Gubitak epidermalnih matičnih ćelija u neposrednoj blizini oboda rane imaza posledicu aktivaciju gena koji stimulišu visoku proliferaciju keratinocita,smanjen potencijal za njihovu migraciju i nemogućnost zarastanja rana.Ključne reči: hronični venski ulkusi; epidermalne matične ćelije; mikročip tehnika

Description (srp)

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Description (eng)

The skin is the largest organ of human body and is constantly renewing. Epidermaland hair follicle stem cells (ESC) reside in distinct niches are indispensable to skin homeostasisand wound closure. The non-healing edges of venous ulcers (VUs) are healing-incompetent,consisting of hyper-proliferative and non-migratory keratinocytes implicating possible deregulation of ESCs. The genes regulating ESC niches have been studied primarily in mouse models.We employed transcriptional profiling of tissue skin specimens derived from the non-healingedges of VUs, to identify changes in gene expression leading to deregulation of ESCs and theirfate in a prospective clinical study of 11 patients. We discoeverd and confirmed the suppressionof the following genes: bone morphogenetic protein receptor 1 (BMPR1) and GATA bindingprotein 3 (GATA3) and inhibitors of DNA-binding proteins 2 and 4 (ID2 and ID4). In addition,we found down-regulation of leucine-rich repeats and immunoglobulin-like domains protein 1(LRGIG1), a gene important for maintaining ESCs in a quiescent state, and absence of keratin15 (K15), a marker of the basal stem cell compartment. These data indicated local depletion ofESCs. We also found diminished levels of phosphorylated glycogen synthase kinase 3 (GSK3),nuclear ß-catenin present in keratinocytes and overexpression of its transcriptional target, cmyc, supporting the notion of the activation of the Wnt pathway.We conclude that loss of genes important for regulation of ESCs and their fate alongwith nuclear presence of ß-catenin and c-myc in the VU may lead to the deprivation of localpopulation of ESC and contribute to a hyper-proliferative, non-migratory wound edge and overall impairment of healing.

Object languages

Serbian

Date

2021

Rights

Creative Commons License
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Identifiers