HNF1β protects endometriotic cells against apoptotic cell death by upregulating the expression of anti-apoptotic genes.

The overexpression of hepatocyte nuclear factor 1 beta (HNF1β) in endometriotic lesion has been demonstrated. However, the role of HNF1β in endometriosis remains largely unknown. Human endometriotic 12Z cells showed higher level of HNF1β when compared with normal endometrial HES cells. In human endometriotic 12Z cells, HNF1β knockdown increased susceptibility to apoptotic cell death by oxidative stress, while HNF1β overexpression suppressed apoptosis. In addition, HNF1β knockdown and overexpression significantly decreased and increased, respectively, the expression of NFκB-dependent anti-apoptotic genes. Knockdown of the anti-apoptotic genes significantly reduced the HNF1β-induced resistance against oxidative stress in 12Z cells. Furthermore, HNF1β regulated the transcriptional activity of NFκB, and a NFκB inhibitor suppressed the HNF1β-enhanced NFκB-dependent anti-apoptotic gene expression and the resistance of the 12Z cells against cell death. Taken together, these data suggest that HNF1β overexpression may protect endometriotic cells against oxidative damage by augmenting anti-apoptotic gene expression.