β-Cell-Specific Mafk Overexpression Impairs Pancreatic Endocrine Cell Development

Abstract

The MAF family transcription factors are homologs of v-Maf, the oncogenic component of the avian retrovirus AS42. They are subdivided into 2 groups, small and large MAF proteins, according to their structure, function, and molecular size. MAFK is a member of the small MAF family and acts as a dominant negative form of large MAFs. In previous research we generated transgenic mice that overexpress MAFK in order to suppress the function of large MAF proteins in pancreatic β-cells. These mice developed hyperglycemia in adulthood due to impairment of glucose-stimulated insulin secretion. The aim of the current study is to examine the effects of β-cell-specific Mafk overexpression in endocrine cell development. The developing islets of Mafk-transgenic embryos appeared to be disorganized with an inversion of total numbers of insulin+ and glucagon+ cells due to reduced β-cell proliferation. Gene expression analysis by quantitative RT-PCR revealed decreased levels of β-cell-related genes whose expressions are known to be controlled by large MAF proteins. Additionally, these changes were accompanied with a significant increase in key β-cell transcription factors likely due to compensatory mechanisms that might have been activated in response to the β-cell loss. Finally, microarray comparison of gene expression profiles between wild-type and transgenic pancreata revealed alteration of some uncharacterized genes including Pcbd1, Fam132a, Cryba2, and Npy, which might play important roles during pancreatic endocrine development. Taken together, these results suggest that Mafk overexpression impairs endocrine development through a regulation of numerous β-cell-related genes. The microarray analysis provided a unique data set of differentially expressed genes that might contribute to a better understanding of the molecular basis that governs the development and function of endocrine pancreas.

Structure of the Eurasian moorhen spleen: A comprehensive study using gross anatomy, light, and transmission electron microscopy

“…Splenic macrophages play significant roles in blood filtration (Klei, Meinderts, Berg, & Bruggen, 2017). MafB is a basic leucine zipper transcription factor encoded by the Mafb gene and was found to be required for several processes including macrophage differentiation and islet beta cells development (Abdellatif et al, 2015; Abdellatif et al, 2016; Hamada, Tsunakawa, Jeon, Yadav, & Takahashi, 2020). MafB was also reported to be expressed by large proportion of splenic macrophages in mice (Lloyd, Phillips, Cooper, & Dunbar, 2008).…”

Insights into microstructure and expression of markers of proliferation, apoptosis and T cells in the spleen of cattle egret (Bubulcus ibis)

“…Formalin‐fixed spleens were processed for paraffin embedding. The whole organ was serially sectioned at 4‐μm thickness, and the obtained slides were labelled for subsequent analysis (Abdellatif et al., 2016). For the histological study, paraffin sections were dewaxed, rehydrated and stained with haematoxylin and eosin (H&E) and Masson's trichrome stains (Abdellatif et al., 2022; Suvarna et al., 2019).…”

EXPRESSION OF INSULIN, GLUCAGON, SOMATOSTATIN, AND PANCREATIC POLYPEPTIDE IN THE PANCREAS OF THE EURASIAN MOORHEN (Gallinula chloropus)

“…Seven birds were utilized for identifying different pancreatic lobes and characterizing the histological and histochemical features of the pancreas. The whole pancreas of the three remaining birds was extracted and different lobes were processed for serial sectioning and subsequent screening of islet composition and distribution within the whole organ using immunohistochemistry (12). Pancreases were collected as soon as the birds became completely immobile, trimmed from surrounding tissues, and fixed in 10% neutral buffered formalin.…”