Expression of Wnt, Frizzled, sFRP, and DKK genes in adult human pancreas.
Wnts are important signaling molecules involved in many normal developmental processes in the human body as well as some forms of cancer. Nineteen Wnt genes are found in the human genome, as well as 10 Wnt receptor genes called Frizzled. Two coreceptors called LRP 5 and 6 are critical for Wnt signal transduction. The interaction of the Wnts with the receptors is regulated by two classes of extracellular Wnt or LRP binding proteins called sFRP and Dickkopf (DKK), which modulate Wnt signaling. We have examined the expression of all Wnt family members both in the exocrine portion and in isolated islets of adult human pancreas. RT-PCR analysis of the 1-day cultured exocrine pellet fraction from the islet isolation procedure showed that Wnt 2, 2b, 3, 4, 5a, 5b, 7a, 7b, 14, and 15 were detectable. All 10 Frizzled (Frz) receptors were expressed but only Frizzled 1, 2, 4, 5, and 6 strongly. RT-PCR performed on purified human islets revealed that Wnt 2b, 3, 4, 5a, 7b, 10a, and 14 and Frz 4, 5, and 6 were the most highly expressed. DKK 1, 3, and 4 as well as sFRP 1, 4, and 5 were expressed in the exocrine fraction. sFRP 2 and 3 were detectable but only at low levels. In situ hybridization for Frz 1-7 showed that expression colocalized with the islets of Langerhans. Together the data suggest that active Wnt signaling occurs in adult pancreas and is probably important for physiological functions.
Heller
R Scott
RS
JDRF Center for Beta Cell Therapy, Europe. shll@hagedorn.dk
Klein
Tino
T
Ling
Zhidong
Z
Heimberg
Harry
H
Katoh
Masaru
M
Madsen
Ole D
OD
Serup
Palle
P
D000293:Adolescent; D000328:Adult; D000818:Animals; D005260:Female; D051157:Frizzled Receptors; D015870:Gene Expression; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D007328:Insulin / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051153:Wnt Proteins; D051154:Wnt2 Protein; D029961:Zebrafish Proteins; D000094742:Secreted Frizzled-Related Proteins
D051157:Frizzled Receptors; D005934:Glucagon; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012313:RNA; D051153:Wnt Proteins; D051154:Wnt2 Protein; D029961:Zebrafish Proteins; C501126:DKK1 protein, human; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins; C495244:WNT2 protein, human; C501128:dkk1b protein, zebrafish