Negative Interplay of Retinoic Acid and TGF‐β Signaling Mediated by TG‐Interacting Factor to Modulate Mouse Embryonic Palate Mesenchymal–Cell Proliferation

Mesenchymal‐cell proliferation is the main process in shelf outgrowth. Both all‐trans‐retinoic acid (atRA) and transforming growth factor‐β3 (TGF‐β3) play an important role in mouse embryonic palate mesenchymal (MEPM) cell proliferation. In the present study, we investigated the crosstalk between RA and TGF‐β signaling in MEPM‐cell proliferation. We found that atRA inhibited MEPM‐cell proliferation by downregulating TGF‐β/Smad signaling and that TGF‐β3 treatment was able to antagonize RA signaling. Transforming growth–interacting factor (TGIF) is a transcriptional repressor that suppresses both TGF‐β‐ and retinoid‐driven gene transcription. Furthermore, we investigated the role of TGIF in the interaction between both TGF‐β and RA signaling in MEPM‐cell proliferation. The results showed that both atRA and TGF‐β3 significantly increased the expression level of TGIF, and TGIF mediated the negative interaction between TGF‐β and RA signaling pathways, which depended on TGIF binding to Smad2 or RARβ (RA receptor beta). Moreover, after deletion of TGIF, both the effects of atRA on TGF‐β‐dependent protein expression and the effects of TGF‐β on RA‐dependent protein expression were lost. So we conclude that there is a negative functional interplay of RA and TGF‐β signaling mediated by TGIF to modulate MEPM‐cell proliferation
Source: Birth Defects Research Part B: Developmental and Reproductive Toxicology - Category: Perinatology & Neonatology Authors: Tags: Research Article Source Type: research