The proliferative effects of Pyropia yezoensis peptide on IEC-6 cells are mediated through the epidermal growth factor receptor signaling pathway

Abstract

For a number of years, seaweed has been used as a functional food in Asian countries, particularly in Korea, Japan and China. Pyropia yezoensis is a marine red alga that has potentially beneficial biological activities. In this study, we examined the mechanisms through which a Pyropia yezoensis peptide [PYP1 (1–20)] induces the proliferation of IEC-6 cells, a rat intestinal epithelial cell line, and the involvement of the epidermal growth factor receptor (EGFR) signaling pathway. First, cell viability assay revealed that PYP1 (1–20) induced cell proliferation in a concentration-dependent manner. Subsequently, we examined the mechanisms responsible for this induction of proliferation induced by PYP1 (1–20). EGFR is widely expressed in mammalian epithelial tissues, and the binding of this ligand affects a variety of cell physiological parameters, such as cell growth and proliferation. PYP1 (1–20) increased the expression of EGFR, Shc, growth factor receptor-bound protein 2 (Grb2) and son of sevenless (SOS). EGFR also induced the activation of the Ras signaling pathway through Raf, MEK and extracellular signal-regulated kinase (ERK) phosphorylation. In addition, cell cycle analysis revealed the expression of cell cycle-related proteins. The results demonstrated an increased number of cells in the G1 phase and an enhanced cell proliferation. In addition, the upregulation of cyclin D, cyclin E, Cdk2, Cdk4 and Cdk6 was observed accompanied by a decreased in p21 and p27 expression. These findings suggest that PYP1 (1–20) stimulates the proliferation of rat IEC-6 cells by activating the EGFR signaling pathway. Therefore, PYP1 (1–20) may be a potential source for the development of bio-functional foods which promotes the proliferation of intestinal epithelial cells.

Proteins and Carbohydrates from Red Seaweeds: Evidence for Beneficial Effects on Gut Function and Microbiota

“…Food derived bioactive peptides have been shown to modulate intestinal epithelial cell differentiation and cytokine production [ 76 ]. Among these, a bioactive peptide derived from Porphyra yezoensis , termed PY-PE or PYP1, whose sequence is A-L-E-G-G-K-S-S-G-G-G-E-A-T-R-D-P-E-P-T, has been shown to induce the proliferation of IEC-6 cells, a rat intestinal epithelial cell line [ 77 , 78 ]. The stimulation of two different molecular signaling pathways has been found to be involved in this effect.…”

“…Epidermal growth factor (EGF) is an important factor in the regulation of MBF, as it stimulates epithelial cell growth, proliferation and differentiation by binding to its receptor (EGFR) and the subsequent activation of several signaling pathways. PY-PE has been shown to increase the expression of EGFR and the adaptor molecules Shc, growth factor receptor bound 2 (Grb2) and Son of Sevenless (SOS), and to activate the Ras/Raf/mitogen activated protein kinase (MAPK)-ERK kinase (MEK)/extracellular signal-regulated kinases (ERK) pathway (Ras/Raf/MEK/ERK) [ 77 ]. The final effect is the recruitment of cells into G1 phase, with an increased expression of cyclins D and E, cyclin dependent kinase (CDK) 2, 4 and 6, and a decrease in the expression of cell cycle inhibitors p21 and p27.…”

Protective effect of Pyropia yezoensis glycoprotein on chronic ethanol consumption-induced hepatotoxicity in rats

“…Pyropia yezoensis, a species of marine algae, has long been consumed in Korea, Japan and China. It has a range of biological activities, including cell proliferation (21), antioxidation (22) and antiinflammatory effects (23). In the present study, the in vivo protective effect of P. yezoensis on chronic ethanol consumption-induced liver injury was investigated in mice.…”

Chemoprotective effects of a recombinant protein from Pyropia yezoensis and synthetic peptide against acetaminophen-induced Chang liver cell death

“…Currently, only one study using a particular PYP peptide has reported its regulation of multiple cell growth-related signals in MCF-7 cells ( 25 ). PYP has also been shown to stimulate the proliferation of IEC-6 normal intestinal epithelial cells and is associated with the insulin-like growth factor I (IGF-IR) and epidermal growth factor receptor (EGFR) signaling pathways ( 26 , 27 ).…”