Effect of HDAC3 on pelvic fibrosis and TGF-β1 expression in endometriosis
SU Leng-man
SUI Dong-yuan
ZHANG Xin-yue
LU Jian-jun
Abstract：Objective To investigate the role of histone deacetylase 3(HDAC3)in pelvic fibrosis and intrauter-ine adhesions in endometriosis(EM),and to explore its regulatory mechanism.Methods From March 2023 to June 2024,30 eutopic endometrium samples and 30 ectopic endometrium samples were collected from EM patients,designated as EM-eutopic and EM-ectopic groups,respectively.The control group included 30 age-matched women without EM undergoing surgery for non-hormone-dependent benign ovarian tumors.Immunohistochemistry was used to detect HDAC3 and TGF-β1 expression.Pelvic adhesions were evaluated using the revised American Fertility Society(r-AFS)scoring system.An EM rat model was established,and HDAC3,TGF-β1,α-smooth muscle actin(α-SMA),colla-gen expression,and fibrosis area were dynamically observed from day 0 to 21.Pearson correlation analysis assessed rela-tionships among these indicators.In vitro,human endometriotic epithelial 12Z cells were subjected to HDAC3 overexpres-sion or inhibition to detect changes in TGF-β1,collagen,and α-SMA.Dual-luciferase reporter assays were per-formed to evaluate the effect of HDAC3 on TGF-β1 promoter activity.Results Compared with controls,the EM-eu-topic group showed significantly higher TGF-β1 expression and r-AFS scores(P＜0.05).EM-ectopic tissues exhibi-ted further upregulation of HDAC3,with increased TGF-β1 expression and r-AFS scores compared to EM-eutopic tis-sues(P＜0.05).HDAC3 was positively correlated with r-AFS score(r=0.782,P＜0.001),and TGF-β1 expres-sion,dysmenorrhea(r=0.721),and infertility(r=0.685)were significantly associated with r-AFS(all P＜0.001).In rats,HDAC3 expression increased from day 0 to 21,accompanied by elevated TGF-β1,collagen deposition,and fi-brosis area(all P＜0.05).HDAC3 levels were positively correlated with TGF-β1(r=0.824)and fibrosis area(r=0.802)(P＜0.001).In 12Z cells,HDAC3 overexpression increased TGF-β1,collagen,and α-SMA expression(P＜0.05),whereas HDAC3 inhibition decreased their expression(P＜0.05).Luciferase activity was enhanced in the HDAC3 overexpression group and reduced in the HDAC3 inhibition group(P＜0.05).Conclusion Upregulation of HDAC3 is significantly associated with pelvic fibrosis severity and TGF-β1 signaling activation in endometriosis.Modula-ting HDAC3 expression effectively alters TGF-β1,collagen,and α-SMA levels,suggesting HDAC3 as a potential ther-apeutic target for EM-related pelvic fibrosis.
Keywords：histone deacetylase 3endometriosispelvic fibrosispelvic adhesions
Publication Date：2026-01-15
Online Publishing Date：2026-03-04(First online date of this platform, not the publication date of the document)
Pages：9( 14-22 )