Repeated tissue injury and repair and
fibrosis play a pivotal role in
endometriosis. Fibrotic tissue consists of
extracellular matrix proteins, regulated by transcriptional factors promoting cell proliferation and survival.
Periostin is one of the putative key
extracellular matrix proteins. This study aimed to determine whether
transcription factor 21 (TCF21) is involved in the development of
endometriosis as an upstream regulatory gene of
periostin.
Formalin-fixed,
paraffin-embedded tissue samples [normal endometrium of women without
endometriosis; eutopic endometrium of women with
endometriosis; ovarian
endometriosis (OE); and deep infiltrating
endometriosis (DIE)] and respective cells were analyzed. Basal, transiently stimulated, and knocked down
periostin and TCF21 concentrations in stromal cells of women with or without
endometriosis were examined.
Periostin and TCF21 expressions were undetected in normal endometrium of women without
endometriosis, weakly positive in eutopic endometrium of women with
endometriosis, moderately positive in OE, and strongly positive in DIE. Type 2 helper T-cell
cytokines (IL-4,
IL-13, and
transforming growth factor-β1) increased the
mRNA expression of
periostin and TCF21. These
cytokines,
periostin, and TCF21 colocalized in the stroma of OE and DIE.
siRNA against human TCF21 gene suppressed
periostin expression. Transfection of TCF21 plasmid vector into stromal cells of women without
endometriosis, which originally expressed neither
periostin nor TCF21, resulted in TCF21 and
periostin expression. TCF21 and
periostin are involved in the regulation of
fibrosis in
endometriosis. TCF21 may be a promising therapeutic target and
biomarker in
endometriosis.