Effects of retinoic acid on the β-catenin/TCF pathway in culture porcine tracheobronchial epithelial cells

Abstract

The effects of retinoic acid on the β-catenin/TCF pathway in cultured porcine tracheo-bronchial epithelial cells (TBEC) were investigated. After TBEC were treated with retinoic acid at various concentrations, mRNA and protein changes of β-catenin in cytoplasm, nucleus and whole cell of the TBEC were observed by immunocytochemical stain, RT-PCR and Western blotting. And the changes of the target gene cyclinD1 of β-catenin/TCF pathway were also observed. It was found that there was no significant difference in β-cat mRNA level after retinoic acid treatment. However, the expression of β-catenin in the whole cell and cytoplasm was elevated with the increase of retinoic acid concentration (P<0.01). The nuclear protein β-catenin and target gene cyclinD1 of β-catenin/TCF pathway was decreased (P<0.05). It was indicated that retinoic acid could increase β-catenin level of the whole cell protein and decreased nuclear β-catenin, downregulating β-cat/TCF signaling activity and reducing target gene cyclinD1 protein level. As a result, retinoic acid can downregulate β-catenin/TCF pathway in porcine tracheobronchial epithelial cell, suggesting that retinoic acid can inhibit the proliferation and accelerate differentiation of tracheobronchial epithelial cells.

Keywords

β-catenin / retinoic acid / cyclinD1 / tracheobronchial epithelial cells

References

[1] ChenF, WuR L, WangX, et al.. Effects of cigarette smoke extract on the expression of beta-cat and tyrosine phosphorylation in airway epithelial cell. Chin Med J (Chinese), 2001, 81: 406-406

[2] XiaoJ H, GhosnC, HinchmanC. Adenomatous polyposis coli (APC)-independent regulation of beta-catenin degradation via a retinoid X receptor-mediated pathway. J Biol Chem, 2003, 278(32): 29954-29954

[3] UemuraK, KitagawaN, KohnoR, et al.. Presenilin 1 mediates retinoic acid—induced differentiation of SH-Sy5y cells through facilitation of wnt signaling. J Neurosci Res, 2003, 73: 166-166

[4] KitagawaM, HatakeyamaS, ShiraneM, et al.. An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of beta-catenin. EMBO J, 1999, 18: 2401-2401

[5] ShtutmanM, ZhurinskyJ, SimchaI, et al.. The cyclinD1 gene is a target of the beta-catenin/lef-1 pathway. Proc Natl Acad Sci USA, 1999, 96(10): 5522-5522

[6] EaswaranV, PishvaianM, Salimuddin, et al.. Cross-regulation of β-catenin-Lef/Tef and retinoid signaling. Current Biology, 1999, 9(23): 1415-1415

[7] NabeyratE, BesnardV, CorroyerS, et al.. Retinoic acid-induced proliferation of lung alveolar epithelial cell: relation with the IGF system. Am J Physiol, 1998, 275(1 Pt 1): L71-L71