Role of MIF and its antagonist ISO-1 in the pathogenesis of pathological scars / 实用医学杂志

ABSTRACT

Objective To explore the role of macrophage migration inhibitory factor (MIF) in the pathogenesis of pathological scar and the effect of ISO-1 on the behavior of scar fibroblasts.Methods Samples of normal skin,normal scar,and pathological scar were collected and detected by hematoxylin-eosin staining and immumohistochemical staining.Human fibroblasts were isolated from the samples and then divided into different groups with the intervention with ISO-1 (0 ～ 100 μ mol/mL).Fibroblast proliferation was detected by Alamber dyeing and cell apoptosis was detected by TUNEL staining.Expressions of fibroblast specific proteins and PI3K/Akt/mTOR signaling pathways wcre detected by Western Blot and RT-PCR.Results The positive rates of MIF for hyperplastic scar and keloid were greater than those for normal scar and normal skin (P ＜ 0.01).Apoptotic cells occurred less in the group without intervention.The apoptotic rate increased gradually as the concentration of ISO-1 increased.There were significant statistical differences in the migration rate among all the groups (P ＜ 0.05).As concentration of ISO-1 increased,the protein and gene expressions of type I collagen,FN and CTGF were decreased.Expressions of activated PI3K and Akt decreased as ISO-1 concentration increased.Conclusions The expression of MIF is different in different types of scar tissue.ISO-1 inhibits the biological behavior of fibroblasts derived from pathological scar through PI3K/Akt/mTOR pathways.