Regulatory effects of angiotensin II on differentiation of mesenchymal stem cells to keratinocytes

Abstract

Objective To investigate the effect of angiotensinⅡ(AngⅡ)on the differentiation of bone marrow mesenchymal stem cells(BMSCs) to keratinocytes and the signal mechanism. Methods The BMSCs from Wistar rats were isolated. The expression of BMSCs surface antigens was detected by flow cytometry. The secretion concentration of AngⅡwas detected by enzyme linked immunosorbent assay(ELISA).The expression of keratin 10(K10)was detected by immunocytochemistry after keratinocyte induction. The effects of AngⅡ, Losartan, PD123319 and their downstream signal molecule blockers on the number of K10 positive cells after keratinocyte induction by BMSCs were observed. Results The positive rate of BMSCs surface markers CD29 and CD90 was 99% or above.The positive rate of CD34 and CD45 was less than 2%.The concentration of AngⅡin cell supernatant showed an increasing trend with the increase of incubation time(P< 0.05).The K10 positive rate of BMSCs in keratinocyte induction group given AngⅡin 7 and 14 days was 69.02% and 82.10% respectively, which was obviously higher than that in control group(P< 0.05).The number of positive K10 cells treated with Losartan, SB203580, AG490, or SP600125 was reduced. Conclusion AngⅡcould significantly increase the conversion rate of BMSCs to keratinocytes.p38 mitogen activated protein kinase(p38MAPK), janus kinase 2/3(JAK2/3)and c- Jun N- terminal kinase(JNK) signal pathways were closely related with the role mediated by AngⅡ. AngⅡpromoted BMSCs to convert into keratinocytes, which might be one of the mechanisms of promoting wound epithelialization. Key words: AngiotensinⅡ; Mesenchymal stem cells; Keratinocyte; Wound healing