He Ting, Bai Xiaozhi, Yang Longlong, Fan Lei, Li Yan, Su Linlin, Gao Jianxin, Han Shichao, Hu Dahai
Cell Physiol Biochem. 2015;37(2):666-76. doi: 10.1159/000430385.
BACKGROUND/AIMS: Our previous study confirmed that Loureirin B (LB) can inhibit hypertrophic scar formation. However, the mechanism of LB-mediated inhibition of scar formation is still unknown.
Immunohistochemistry was used to detect expression of Col1, FN and TGF-β1 in skin and scar tissue. Fibroblasts were stimulated with TGF-β1 to mimic scar formation. LB or MAPK inhibitors were used to study the pathways involved in the process. Western blotting was used to evaluate the expression of p-JNK, p-ERK, p-p38, Col1 and FN. The contractile capacity of fibroblasts was evaluated using a gel contraction assay. Tissues were cultured ex vivo with LB to further investigate the participation of ERK and JNK in the LB-mediated inhibition of scar formation.
FN and Col1 were up regulated in hypertrophic scars. LB down regulated p-ERK and p-JNK in TGF-β1-stimulated fibroblasts, while levels of phosphorylated p38 did not change. The down regulation of p-ERK and p-JNK was associated with a reduction of Col1 and FN. Similarly, inhibition of ERK and JNK down regulated the expression of Col1 and FN in TGF-β1-stimulated fibroblasts. LB down regulated protein levels of p-ERK and p-JNK in cultured hypertrophic scar tissue ex vivo.
This study suggests that LB can inhibit scar formation through the ERK/JNK pathway.
背景/目的:我们之前的研究证实了龙血素B(LB)可抑制增生性瘢痕形成。然而,LB介导抑制瘢痕形成的机制仍不清楚。
采用免疫组织化学法检测皮肤和瘢痕组织中I型胶原(Col1)、纤连蛋白(FN)和转化生长因子-β1(TGF-β1)的表达。用TGF-β1刺激成纤维细胞以模拟瘢痕形成。使用LB或丝裂原活化蛋白激酶(MAPK)抑制剂来研究该过程中涉及的信号通路。采用蛋白质免疫印迹法评估磷酸化c-Jun氨基末端激酶(p-JNK)、磷酸化细胞外信号调节激酶(p-ERK)、磷酸化p38、Col1和FN的表达。使用凝胶收缩试验评估成纤维细胞的收缩能力。用LB对组织进行离体培养,以进一步研究细胞外信号调节激酶(ERK)和c-Jun氨基末端激酶(JNK)在LB介导的抑制瘢痕形成中的作用。
增生性瘢痕中FN和Col1上调。LB下调了TGF-β1刺激的成纤维细胞中p-ERK和p-JNK的表达,而磷酸化p38的水平没有变化。p-ERK和p-JNK的下调与Col1和FN的减少有关。同样,抑制ERK和JNK可下调TGF-β1刺激的成纤维细胞中Col1和FN的表达。LB下调了离体培养的增生性瘢痕组织中p-ERK和p-JNK的蛋白水平。
本研究表明,LB可通过ERK/JNK信号通路抑制瘢痕形成。