Novel mechanism of tumorigenesis: increased transforming growth factor-beta 1 suppresses the expression of connexin 43 in BALB/cJ mice after implantation of poly-L-lactic acid.
Poly-L-lactic acid (PLLA) is a widely used promising material for surgical implants such as tissue-engineered scaffolds. In this study, we aimed to determine the in vivo effect of PLLA plates on the cellular function of subcutaneous tissue in the two mouse strains, BALB/cJ and SJL/J, higher and lower tumorigenic strains, respectively. Gap-junctional intercellular communication (GJIC) and the expression of connexin 43 (Cx43) protein were significantly suppressed, whereas the secretion of transforming growth factor-beta 1 (TGF-beta 1) level was significantly increased in PLLA-implanted BALB/cJ mice compared with BALB/cJ controls. However, no significant difference in TGF-beta 1 secretion was observed between the SJL/J-implanted and SJL/J control mice. We found for the first time that a significant difference was observed between the two strains; thus, the PLLA increased the secretion of TGF-beta 1 and suppressed the mRNA expression of Cx43 at the earlier stage after implantation into the higher-tumorigenic strain, BALB/cJ mice. This novel mechanism might have a vital role in the inhibition of GJIC and promote the tumorigenesis in BALB/cJ mice.
Ahmed
Saifuddin
S
Division of Medical Devices, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya ku, Tokyo 158-8501, Japan.
Tsuchiya
Toshie
T
D000818:Animals; D001483:Base Sequence; D001672:Biocompatible Materials / Q000633:toxicity*; D002450:Cell Communication; D018031:Connexin 43 / Q000235:genetics*; D005260:Female; D017629:Gap Junctions / Q000502:physiology; D015870:Gene Expression; D019344:Lactic Acid / Q000633:toxicity*; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000209:etiology*; D011091:Polyesters; D011108:Polymers / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D001672:Biocompatible Materials; D018031:Connexin 43; D011091:Polyesters; D011108:Polymers; D012333:RNA, Messenger; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019344:Lactic Acid; C033616:poly(lactide)