A novel role of angiotensin II in epidermal cell lineage determination: Angiotensin II promotes the differentiation of mesenchymal stem cells into keratinocytes through the p38 MAPK, JNK and JAK2 signalling pathways.
Exp Dermatol
; 28(1): 59-65, 2019 01.
Article
em En
| MEDLINE
| ID: mdl-30412649
ABSTRACT
BACKGROUND:
Recent evidence suggests that angiotensin II (Ang II) plays a role in cutaneous wound healing. Mesenchymal stem cells (MSCs) are known as a rich source of cells that re-establish healed skin. However, the potential impact of Ang II on MSC differentiation into keratinocytes is still unknown.OBJECTIVE:
The present study was conducted to explore the effect of Ang II on the differentiation of bone marrow-derived MSCs (BM-MSCs) into keratinocytes.METHODS:
Bone marrow-derived MSCs were isolated from rat bone marrow and cultured. The expression of Ang II type 1 (AT1 ) and type 2 (AT2 ) receptors was examined by immunofluorescence staining. The differentiation of BM-MSCs into keratinocytes was investigated by flow cytometry or/and histological observation.RESULTS:
The BM-MSCs constitutively expressed both AT1 and AT2 receptors. The differentiation of BM-MSCs into keratinocytes was successfully induced. Interestingly, incubation of BM-MSCs with Ang II further promoted the differentiation of BM-MSCs into keratinocyte, which was abolished by pretreament with losartan, an AT1 receptor antagonist, but not by PD123319, an AT2 receptor antagonist. Moreover, the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580, the c-Jun N-terminal kinase (JNK) inhibitor SP600125 and the Janus-activated kinase (JAK)2 inhibitor AG490 suppressed Ang II-induced differentiation of BM-MSCs into keratinocytes. The phosphoinositide-3 kinase (PI3K) inhibitor wortmannin and MEK1/2 inhibitor U0126 had no effect on BM-MSC differentiation into keratinocytes.CONCLUSIONS:
Our data demonstrated for the first time that Ang II plays a promotive role in the differentiation of BM-MSC into keratinocytes through the AT1 receptor, and that the p38 MAPK, JNK and JAK2 signalling pathways are involved in this process.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Angiotensina II
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Queratinócitos
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Diferenciação Celular
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Linhagem da Célula
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Sistema de Sinalização das MAP Quinases
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Células-Tronco Mesenquimais
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article