Intramucosal distribution of WNT signaling components in human esophagus.
BACKGROUND
The molecular mechanisms governing the biology and pathobiology of esophageal squamous mucosa in health and disease are not completely understood. Earlier genome-wide expression study of normal-looking esophageal squamous mucosa has shown differential expression of the Wingless-type MMTV integration site family (Wnt) modulators Dickkopf (Dkk) homologs among healthy individuals and patients with reflux esophagitis and Barrett metaplasia suggesting that the Wnt pathway may be involved in esophageal mucosal biology.


METHODS
Seven full-thickness human donor esophagi were cryosectioned for immunohistochemical analysis, and lamina propria (LP), basal (BC), intermediate (IC), and superficial (SC) cells were also dissected by laser-capture microdissection for real-time polymerase chain reaction.


RESULTS
Wnt1, 2b, and 3a were expressed primarily in BC, Wnt3, and 5b in LP, and Wnt5a in IC. Frizzled 1, low-density lipoprotein receptor-related protein 6, secreted frizzled-related protein 1, T-cell-specific transcription factor 3, and dishevelled 3 were expressed highest in LP decreasing precipitously medially toward SC. Dkk1 predominantly expressed in SC was more than 100-folds greater than other layers (P<0.001). Dkk4 was expressed primarily in SC but Dkk3 was opposite with greatest expression in LP. Immunohistochemical analysis showed Wnt1 and 3a in BC, Wnt5a in IC and SC, Dkk1 predominantly in SC, Dkk4 in SC and IC, and Dkk3 and SFRP1 in LP and BC
Ali
Irshad
I
Division of Gastroenterology and Hepatology, MCW Dysphagia Institute, Digestive Disease Center, Medical Collegeof Wisconsin, Milwaukee, WI 53226, USA.
Rafiee
Parvaneh
P
Zheng
Yue
Y
Johnson
Christopher
C
Banerjee
Banani
B
Haasler
George
G
Jacob
Howard
H
Shaker
Reza
R
D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; D004848:Epithelium / Q000378:metabolism*; D004947:Esophagus / Q000166:cytology / Q000378:metabolism*; D051157:Frizzled Receptors / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007834:Lasers; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism; D042282:Microdissection; D009092:Mucous Membrane / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D000094742:Secreted Frizzled-Related Proteins
D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; D051157:Frizzled Receptors; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; C498624:DKK3 protein, human; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins