Abstract
BackgroundMilk is a rich source of natural growth factors that may support oral tissue homeostasis and wound healing. We had shown earlier that blocking TGF-β receptor type I kinase with the inhibitor SB431542 abolished the expression of IL11 and other genes in human gingival fibroblasts exposed to the aqueous fraction of milk. Our aim was to identify the entire signature of TGF-β receptor type I kinase-dependent genes regulated by the aqueous fraction of human milk.ResultRNAseq revealed 99 genes being strongly regulated by milk requiring activation of the SB431542-dependent TGF-β receptor type I kinase. Among the SB431542-dependent genes is IL11 but also cadherins, claudins, collagens, potassium channels, keratins, solute carrier family proteins, transcription factors, transmembrane proteins, tumor necrosis factor ligand superfamily members, and tetraspanin family members. When focusing on our candidate gene, we could identify D609 to suppress IL11 expression, independent of phospholipase C, sphinosine-1 phosphate synthesis, and Smad-3 phosphorylation and its nuclear translocation. In contrast, genistein and blocking phosphoinositide 3-kinases by wortmannin and LY294002 increased the milk-induced IL11 expression in gingival fibroblasts.ConclusionTaken together, our data revealed TGF-β receptor type I kinase signaling to cause major changes of the genetic signature of gingival fibroblasts exposed to aqueous fraction of human milk.
Highlights
Milk being the hallmark of mammalian evolution contains the entire spectrum of nutrients that newborns require for their growth and development [1]
Taken together, our data revealed transforming growth factor (TGF)-β receptor type I kinase signaling to cause major changes of the genetic signature of gingival fibroblasts exposed to aqueous fraction of human milk
RNA sequencing of gingival fibroblasts exposed to milk To identify the most strongly regulated genes in gingival fibroblasts exposed to 5% of the aqueous fraction of human milk, an RNA sequencing approach was conducted
Summary
Milk being the hallmark of mammalian evolution contains the entire spectrum of nutrients that newborns require for their growth and development [1]. To detect the TGF-β activity of milk and dairy products, cells responding to TGF-β by an increased expression of target genes can be used [14,15,16]. Further support for the TGF-β activity of milk is provided by the TGF-β receptor type I kinase inhibitor SB431542 [17, 18] In this setting, SB431542 abolished the potential of milk to increase the expression of IL11 [14, 15]. We had shown earlier that blocking TGF-β receptor type I kinase with the inhibitor SB431542 abolished the expression of IL11 and other genes in human gingival fibroblasts exposed to the aqueous fraction of milk. Our aim was to identify the entire signature of TGF-β receptor type I kinase-dependent genes regulated by the aqueous fraction of human milk
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