Epidermal growth factor induces adult human islet cell dedifferentiation

Abstract

Given the inherent therapeutic potential of the morphogenetic plasticity of adult human islets, the identification of factors controlling their cellular differentiation is of interest. The epidermal growth factor (EGF) family has been identified previously in the context of pancreatic organogenesis. We examined the role of EGF in an in vitro model whereby adult human islets are embedded in a collagen gel and dedifferentiated into duct-like epithelial structures (DLS). We demonstrated that DLS formation was EGF dependent, while residual DLS formation in the absence of added EGF was abrogated by EGF receptor inhibitor treatment. With respect to signaling, EGF administration led to an increase in c-Jun NH2-terminal kinase (JNK) phosphorylation early in DLS formation and in AKT and extracellular signalregulated kinase (ERK) phosphorylation late in the process of DLS formation, concomitant with the increased proliferation of dedifferentiated cells. In the absence of EGF, these phosphorylation changes are not seen and the typical increase in DLS epithelial cell proliferation seen after 10 days in culture is attenuated. Thus, in our model, EGF is necessary for islet cell dedifferentiation, playing an important role in both the onset of DLS formation (through JNK) and in the proliferation of these dedifferentiated cells (through AKT and ERK).

Preliminary Investigation on the Effect of <i>Lactobacillus</i> and Epidermal Growth Factor on Tight Junction Proteins in Experimental Clostridium <i>difficile</i> Infection

“…EGF plays an important role in the regulation of cell growth, proliferation and differentiation [20] and promotes epithelial proliferation in adult gut [21]. The potential value of using EGF as a therapeutic tool to treat gastrointestinal injury has been raised previously by some investigators [10] [22].…”

Extract of white button mushroom affects skin healing and angiogenesis

“…Along with the increase in VEGF level and amounts of blood vessels, the extract of mushroom further led to increase in epidermal growth factors, proliferative cells (i.e., PCNA reaction), and collagen fibers as evident by Sirius red staining; and at the same time, a decrease of TUNEL positive apoptotic cells. Epidermal growth factor was known to increase the proliferation of cells, particularly the dedifferentiated ones (Hanley et al,2011). In this study, the increase of positive EGF sites was found on the epidermis, pointing to increase in proliferation of epidermal cells during healing after addition of this mushroom complex.…”

“…EGF is a growth factor that plays an important role in the regulation of cell growth, proliferation, and differentiation by binding to its receptor. Both epidermal growth factor receptor (Hanley et al,2011) and PCNA (Wai et al,2008) are proliferation markers.…”

Dedifferentiated fat cells: A cell source for regenerative medicine

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