Ganieva U, Nakamura T, Osuka S, et al. - Formalin-fixed, paraffin-embedded tissue samples (normal endometrium of women without endometriosis, NE; eutopic endometrium of women with endometriosis, EE; ovarian endometriosis, OE; deep infiltrating endometriosis, DIE) and respective cells were investigated in order to ascertain whether transcription factor 21 (TCF21) was included in the development of endometriosis as an upstream regulatory gene of periostin. Periostin and TCF21 expressions were undetected, weakly positive, moderately positive, and strongly positive in NE, EE, OE, and DIE, respectively. The mRNA expression of periostin and TCF21 was raised via Th2 type cytokines (interleukin-4, interleukin-13, and transforming growth factor-β1). In the stroma of OE and DIE, these cytokines, periostin, and TCF21 co-localized. Periostin expression was repressed by siTCF21. In stromal cells of women without endometriosis, transfection of TCF21 plasmid vector, which formerly expressed neither periostin nor TCF21, led to TCF21 and periostin expression. In conclusion, in endometriosis, TCF21 and periostin are involved in the regulation of fibrosis. Moreover, in endometriosis, TCF21 could be a promising therapeutic target and biomarker.