Dickkopf-3 is expressed in a subset of adult human pancreatic beta cells.
The Dickkopf (Dkk) gene family of secretory modulators of canonical Wnt/beta catenin signals is involved in the control of stem cell proliferation, homeostasis and differentiation. Bioinformatic data on dkk-1/3 gene expression, indicating high expression levels in the human pancreas, led us to analyze these two proteins in adult human pancreatic tissue. Dkk-1/3 mRNA levels and protein distribution were analyzed in isolated human islets vs. the exocrine/ductal pancreatic cells and in paraffin sections of adult human pancreata. Using real time PCR only lowest amounts of dkk-1 mRNA were detectable in the endocrine fractions. Immunohistochemistry did not reveal any Dkk-1 protein in adult human pancreatic tissue. Interestingly, Dkk-3 mRNA and protein were clearly present in adult human pancreatic islets. Messenger RNA levels for Dkk-3 were significantly higher in isolated islets as compared to the exocrine/ductal fraction. Co-staining with an antibody against insulin identified the beta cells of the pancreas as the Dkk-3-positive cells. Notably, only a subset of beta cells contained Dkk-3. As shown by western blot analysis Dkk-3 seems to be proteolytically processed in beta cells. To our knowledge, this is the first study describing a molecule with which the pool of pancreatic beta cells can be further subdivided. Future studies will show whether this sub-classification of beta cells translates into functional differences.
Hermann
M
M
KMT Laboratory, Innsbruck Medical University, Innrain 66, 6020, Innsbruck, Austria. Martin.Hermann@uki.at
Pirkebner
D
D
Draxl
A
A
Berger
P
P
Untergasser
G
G
Margreiter
R
R
Hengster
P
P
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D018925:Chemokines; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000032:analysis / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000737:chemistry / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010179:Pancreas / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D046790:Pancreas, Exocrine / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; C501126:DKK1 protein, human; C498624:DKK3 protein, human; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger