Antisense inhibition of transglutaminase 2 affects development of mouse embryo submandibular gland in organ culture.
Tissue transglutaminase (TGase 2) has been implicated in numerous cellular functions, i.e., apoptosis, differentiation, extracellular matrix protein cross-linking and organogenesis. Earlier report of the strong transient expression of TGase 2 localized at the anchoring sites of muscle bundles of human embryo and recent findings of a similar transient expression of the TGase 2 in the salivary myoepithelial cells of mouse embryo indicated a definitive role of TGase 2 in the cytodifferentiation of myoepithelial cells. To understand functional role(s) of TGase 2 in the organogenesis of salivary gland, antisense inhibition of TGase 2 expression was performed in the organ culture of mouse embryo submandibular gland. The antisense of TGase 2 transfection tested using oral keratinocyte cell line, KB cells, elicited significant inhibition of cellular transglutaminase expression. The same antisense treatment of submandibular glands in organ culture also resulted in the suppression of cellular TGase 2 expression as indicated by weak immunoreaction against anti-TGase 2 in the myoepithelial cells of submandibular glands in contrast to strong reaction in those of the normal and sense-treated glands. Antisense to TGase 2 treatment induced retarded growth of salivary epithelium in 1 week and severe aberrant growth of salivary ducts and acini in 2 weeks and also expression of apoptotic inducer, Bax specifically localized in the myoepithelial cells, suggesting apoptotic state of myoepithelial cells. These data suggest that the antisense inhibition of TGase 2 expression affects the cytodifferentiation of ductal cells and myoepithelial cells, and resulted in severe retardation of tubuloalveolar structure formation of salivary gland.
Lee
Suk Keun
SK
Department of Oral Pathology, College of Dentistry, Kangnung National University, Gangneung 210-702, Republic of Korea.
Kim
Yeon Sook
YS
Lee
Sang Shin
SS
Lee
Young Joon
YJ
Song
In Sun
IS
Park
Sang Chul
SC
Chi
Je Geun
JG
Chung
Soo Il
SI
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007624:KB Cells; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D009924:Organ Culture Techniques; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013363:Submandibular Gland / Q000196:embryology*; D011503:Transglutaminases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000032:analysis / Q000235:genetics
D016376:Oligonucleotides, Antisense; D051028:bcl-2-Associated X Protein; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins