The effects of retinoid status on TGF beta expression during mouse embryogenesis.
In a previous study we investigated the effects of RA excess on TGF beta protein localization in early postimplantation stages of mouse development. Here we extend this investigation by comparing the effects of retinoid deficiency with those of excess, and by comparing the effects of altered retinoid status on TGF beta protein and RNA transcript distribution. In vitamin A-deficient embryos, TGF beta 1 RNA and protein distribution were both unaltered compared with controls; conversely, TGF beta 2 protein levels were reduced while RNA levels remained normal. In RA-treated embryos, the previous study showed that intracellular TGF beta 1 levels were decreased, while those of extracellular TFG beta 1 were initially decreased but subsequently increased; here we found that TGF beta 1 RNA transcript levels were reduced following exposure to RA excess. TGF beta 2 showed a clear disparity between the effects of RA excess on protein and RNA transcript levels: RNA transcript distribution was unchanged or showed a slight increase in RA-treated embryos, whereas the previous results showed greatly reduced protein levels. The new results provide further evidence for interaction between retinoids and TGF beta s during mouse development, and indicate that retinoids are capable of differentially regulating TGF beta isoforms through mechanisms involving different stages in the process of TGF beta synthesis and secretion. The long-term nature of the effects of transient exposure to RA excess suggests that the mechanisms of RA-TGF beta interaction may be indirect.
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D004622:Embryo, Mammalian / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000032:analysis; D011247:Pregnancy; D014176:Protein Biosynthesis / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000187:drug effects / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology*; D014802:Vitamin A Deficiency / Q000503:physiopathology*
D010455:Peptides; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014212:Tretinoin