Excessive retinoic acid inhibit mouse embryonic palate mesenchymal cell growth through involvement of Smad signaling
2017
Huanhuan Zhang, Zhengzhou University, Zhengzhou, People's Republic of China | Xiaozhuan Liu, Zhengzhou University, Zhengzhou, People's Republic of China | Zhan Gao, Zhengzhou University, Zhengzhou, People's Republic of China | Zhitao Li, Henan University of Science and Technology, Luoyang, People's Republic of China | Zengli Yu, Zhengzhou University, Zhengzhou, People's Republic of China | Jun Yin, Zhengzhou University, Zhengzhou, People's Republic of China | Yuchang Tao, Zhengzhou University, Zhengzhou, People's Republic of China | Lingling Cui, Zhengzhou University, Zhengzhou, People's Republic of China
All-trans retinoic acid (atRA), the oxidative metabolite of retinoic acid (RA), is essential for palatogenesis. Overdose RA is capable of inducing cleft palate in mice and humans. Normal embryonic palatal mesenchymal (EPM) cell growth is crucial for shelf growth. Smad signaling is involved in many biological processes. However, it is not much clear if atRA could affect Smad signaling during EPM cells growth. In this study, the timed pregnant mice with maternal administration of 100 mg/kg body weight of RA by gastric intubation were cervical dislocation executed to evaluate growth changes of palatal shelves by hematoxylin and eosin (H and E) staining. At the same time, a primary mouse EPM (MEPM) cell culture model was also established. MEPM cells were treated with atRA (0.1, 0.5, 1, 5 and 10 μM) for 24, 48 and 72 h. The results indicated that the sizes of the shelves were smaller than those in control. AtRA inhibited MEPM cell growth with both increasing concentration and increasing incubation time, especially at 72 h in vitro. Moreover, atRA significantly increased the mRNA and protein expression levels of Smad7 (P less than .05), but the mRNA and protein expression levels of PCNA were reduced (P less than .05). We also found atRA inhibited phosphorylation of Smad2 compared with untreated group (P less than .05). However, the protein and mRNA levels of Smad2 did not change both in atRA-treated and untreated group (P greater than .05). We demonstrated that RA induced inhibition of MEPM cell growth that could cause cleft palate partly by down-regulation of Smad pathway.
Mostrar más [+] Menos [-]Palabras clave de AGROVOC
Información bibliográfica
Este registro bibliográfico ha sido proporcionado por Korea Agricultural Science Digital Library
