AhR-E2F1-KGFR signaling is involved in KGF-induced intestinal epithelial cell proliferation

Keratinocyte growth factor (KGF) stimulates intestinal epithelial cell proliferation upon binding to the KGF receptor (KGFR). The activated aryl hydrocarbon receptor (AhR) serves an important role in the development of tissues by promoting the expression of AhR receptors, which can regulate cell proliferation. In the present study, the signaling pathway between AhR and KGFR in investigated with regards to KGF-induced intestinal epithelial cell proliferation. Male C57BL/6J wild type and AhR(−/−) mice, were randomized into four groups: Control, KGF, AhR(−/−) + KGF and AhR(−/−) (n=6 per group). The small bowel was harvested on day 5 post-treatment. LoVo cells were used to study signaling pathways in vitro and were divided into the following four treatment groups: DMSO, KGF, KGF + small-interfering (si)AhR and siAhR. In vivo, knockdown of AhR mRNA transcripts may abolish KGF-induced intestinal epithelial cell proliferation. Furthermore, KGFR expression was downregulated following knockdown or silencing of AhR expression in vivo and in vitro. The present study identified that the transcription factor E2F1 could regulate KGFR expression, and that siAhR treatment led to reduced expression of E2F1 in the nucleus and inhibited KGF-induced cell proliferation. In conclusion, the current results demonstrated that the AhR-E2F1-KGFR pathway is involved in KGF-induced intestinal epithelial cell proliferation.