AKR1C1介导的复方白蚀片对白癜风角质形成细胞与黑素细胞互作的调控作用OA

Objective To investigate the regulatory effect of Baishi tablets(BST)on the interaction between keratinocytes(KCs)and melanocytes(MCs)in vitiligo,and to explore the role of aldo-keto reductase family 1 member C1(AKR1C1)in inflammation,oxidative stress,and ferroptosis.Methods Primary KCs were isolated from vitiligo lesions and treated with BST(100 μg/ml,48 h),then transcriptome sequencing was performed to identify differentially expressed genes(DEGs).AKR1C1 expression changes were verified by immunofluorescence,qPCR,and Western blotting methods.Overexpression and knockdown models of AKR1C1 were established to evaluate cell proliferation,inflammatory cytokine expression,and JAK2/STAT3 pathway activity.A co-culture system of HaCaT cells and human MCs(PIG1)was further established to assess melanogenesis(tyrosinase,TYR),ferroptosis indicators(Fe2+,Hepcidin),and oxidative stress markers(MDA,GSH-Px).Results Transcriptome analysis identified 184 differentially expressed genes,with BST significantly upregulating antioxidant or metabolism-related genes,such as AKR1C1,HMOX1,and GADD45G(all P＜0.05);while downregulating inflammatory chemokines such as CXCL5,CXCL10,and IL-15(all P＜0.01),which were mainly enriched in IL-17 signaling,steroid hormone biosynthesis,and ferroptosis pathways.The immunofluorescence showed that AKR1C1 expression was reduced in vitiligo lesions(P＜0.001),but significantly restored after BST treatment(P＜0.05).Functional assays demonstrated that AKR1C1 overexpression promoted KC proliferation(P＜0.01)and reduced CXCL9/10,IL-15,and p-JAK2/p-STAT3 levels(all P＜0.05),whereas siRNA knockdown increased inflammatory factors(P＜0.01)and suppressed proliferation(P＜0.01),the effects were partially reversed by BST.In co-culture,AKR1C1 upregulation enhanced TYR expression in MCs(P＜0.01),reduced Fe2+and MDA levels(both P＜0.01),and increased GSH-Px activity(P＜0.01);and BST further enhanced these effects.Conversely,AKR1C1 knockdown exerted opposite changes,which were partially restored by BST(all P＜0.05).Conclusion BST promotes MCs function by upregulating AKR1C1 expression in KCs,thereby suppressing inflammatory responses and alleviating oxidative stress and ferroptosis.AKR1C1 plays a key regulatory role in KC-MC interactions and may represent an important therapeutic target for BST to treat vitiligo.