Transient TWEAK overexpression leads to a general salivary epithelial cell proliferation.
OBJECTIVE
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine that has pro-apoptotic, pro-angiogenic and pro-inflammatory effects. In liver, TWEAK leads to proliferation of progenitor oval cells, but not of mature hepatocytes. This study evaluated the hypothesis that TWEAK overexpression in salivary glands would lead to the proliferation of a salivary progenitor cell.


METHODS
A recombinant, serotype 5 adenoviral vector encoding human TWEAK, AdhTWEAK, was constructed, initially tested in vitro, and then administered to male Balb/c mice via cannulation of Wharton's duct. TWEAK expression in vivo was monitored as protein secreted into saliva and serum by enzyme-linked immunosorbent assays. Salivary cell proliferation was monitored by proliferating cell nuclear antigen staining and apoptosis was monitored using TUNEL staining.


RESULTS
AdhTWEAK administration led to a dose-dependent, transient TWEAK protein expression, detected primarily in saliva. Salivary epithelial cell proliferation was generalized, peaking on approximately days 2 and 3. TWEAK expression had no detectable effect on apoptosis of salivary epithelial cells.


CONCLUSIONS
Transient overexpression of TWEAK in murine salivary glands leads to a general proliferation of epithelial cells vs a selective stimulation of a salivary progenitor cell.
Sugito
T
T
Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-1190, USA.
Mineshiba
F
F
Zheng
C
C
Cotrim
A P
AP
Goldsmith
C M
CM
Baum
B J
BJ
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D049109:Cell Proliferation; D000074049:Cytokine TWEAK; D004847:Epithelial Cells / Q000473:pathology*; D005786:Gene Expression Regulation / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D020287:In Situ Nick-End Labeling; D008024:Ligands; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012463:Saliva / Q000737:chemistry; D018987:Salivary Ducts / Q000473:pathology; D013234:Stem Cells / Q000473:pathology; D013363:Submandibular Gland / Q000473:pathology*; D013997:Time Factors; D048069:Tumor Necrosis Factors / Q000032:analysis / Q000097:blood / Q000235:genetics*
D000074049:Cytokine TWEAK; D008024:Ligands; D018809:Proliferating Cell Nuclear Antigen; C109743:TNFSF12 protein, human; D048069:Tumor Necrosis Factors