?1,4-N-Acetylglucosaminyltransferase encoding gene EXTL3 expression pattern in mouse adult and developing tissues with special attention to the pancreas

Abstract

EXTL3 encodes alpha1,4-N-acetylglucosaminyltransferases I and II enzymes, which are involved in chain initiation and elongation of heparan sulfate (HS) biosynthesis. HS proteoglycans are critically involved in a variety of biological phenomena at various levels of complexity in adult and embryonic lives. Dedicated functions of HS proteoglycans are due to variable HS chains that interact with different cellular proteins, and can be regulated by their synthesizing enzymes. EXTL3 protein is also a putative receptor for Reg protein, a growth signal mediator for the beta-cells of the pancreas. The present Northern blot analysis revealed two EXTL3 transcripts (6.2 and 3.4 kb), which were differentially expressed in different mouse adult tissues. The strongest expression was in the adult brain and pancreas. In the adult pancreas, a comparable intensity of both signals was detected. In the embryonic pancreas, the longer transcript was predominant, and showed a biphasic expression pattern with a peak at E11.5, whereas the shorter one showed a steady level of expression throughout the whole period of pancreatic development. By in situ hybridization, the acini of adults and embryos were strong positive for EXTL3 mRNA. Mature islets of Langerhans gave a weak signal, whereas the developing islets showed moderately positive reaction albeit less intense than the acini. In situ hybridization revealed a wide and differential expression pattern of EXTL3 mRNA in embryonic tissues. At the early stages, intense reaction was found in the developing neurons of the brain and spinal cord and in the epithelia of the developing GIT, pancreas, liver and kidney of embryos. Our data suggested that EXTL3 expression is developmentally regulated, and may contribute to the regulated production of HS in different adult and embryonic tissues.

Regulation of pancreatic endocrine cell differentiation by sulphated proteoglycans

“…A decline in glypican expression during development has previously been demonstrated in the embryonic kidney, where HSPGs play a major role [26]. Our results show that, among the genes encoding glycosaminoglycan-modifying enzymes, Hs2st1 is developmentally regulated, in keeping with previous studies of the expression of the gene encoding glycosyl transferase in embryonic mouse pancreas [38]. This enzyme, which is involved in heparan sulphate chain initiation and elongation, reached a peak during epithelial cell proliferation (i.e.…”

Regenerating proteins and their expression, regulation, and signaling

“…Both the rat and human Reg proteins bind with high affinity to the rat Extl3 receptor upon overexpression of its cDNA in CHO cells. In the adult mouse, Extl3 transcripts are detected in the spleen, liver, testis, stomach and heart whereas the strongest expression is noted in the pancreas and brain (126). In E11.5–E18.5 mouse embryos, Extl3 mRNA is present in the neurons, gastrointestinal tract epithelia, liver, kidney, lung and pancreas.…”

Regenerating islet-derived protein 1 inhibits the activation of islet stellate cells isolated from diabetic mice

“…Reg1 inhibits PSC proliferation and migration, and reduces the synthesis and secretion of Col-I, FN, matrix metallopeptidase (MMP)-1 and MMP-2, and the tissue inhibitors (TI) of metalloproteinases TIMP-1 and TIMP-2 [ 20 ]. The putative receptor through which Reg1 exerts its biological effects has been identified as having 97% homology with the human multiple EXTL3 [ 21 , 22 ], which is highly expressed in mouse islets during embryonic development with reduced expression in adult islets [ 23 ], consistent with a role for Reg1/EXLT3 in β-cell expansion and regeneration.…”