Expression patterns of genes critical for SHH, BMP, and FGF pathways during the lumen formation of human salivary glands

Abstract

Sjögren's syndrome or radiotherapy for head and neck cancer leads to the irreversible hypofunction of salivary gland (SG). The stem/progenitor cell-based regenerative strategy has been proven to be the most promising approach to repair the function of SG. The molecular mechanisms that regulate SG morphogenesis, especially during lumen formation, provide valuable hints for establishment of such regenerative strategies. It has been demonstrated that numerous growth factors particularly belonging to SHH, BMP, and FGF signaling pathway are involved in the regulation of lumen formation and have shown protective effects on the SG from irradiation in mouse models. However, it remains elusive whether the expression pattern and function of these signaling molecules are conserved in humans. In this study, we examined the expression patterns of the molecules critical for SHH, BMP, and FGF signaling cascades from the canalicular stage to the terminal bud stage, the key stages for lumen formation, in human SG and compared them with the expression data observed in mice. Our results manifested that genes involved in SHH signaling pathway showed identical expression patterns, while genes involved in BMP as well as FGF pathway exhibited similar but distinct expression patterns in humans to those in the mouse. We concluded that the expression patterns of genes involved in SHH, BMP, and FGF pathways in the development of human SG exhibit high similarity to that in the development of mouse SG during lumen formation, suggesting that the molecular mechanism regulating the morphogenesis of SG during lumen formation may be conserved in mice and humans. Our results will have an implication in the future establishment of stem-cell based approaches for the repair of SG function.

Keywords: Branching morphogenesis; Gene expression; Human salivary gland; Lumen formation.