Loureirin B Inhibits Hypertrophic Scar Formation via Inhibition of the TGF-β1-ERK/JNK Pathway.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
This study suggests that LB can inhibit scar formation through the ERK/JNK pathway.
Ting
T
He
Xiaozhi
X
Bai
Longlong
L
Yang
Lei
L
Fan
Yan
Y
Li
Linlin
L
Su
Jianxin
J
Gao
Shichao
S
Han
Dahai
D
Hu
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000188:drug therapy* / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D012116:Resins, Plant / Q000494:pharmacology*; D046509:Tissue Culture Techniques; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D024042:Collagen Type I; D005353:Fibronectins; D012116:Resins, Plant; D053773:Transforming Growth Factor beta1; D048051:p38 Mitogen-Activated Protein Kinases; C505764:loureirin B