Lithium chloride promotes mesenchymal-epithelial transition in murine cutaneous wound healing via inhibiting CXCL9 and IGF2.

Cutaneous wound healing is a challenge in plastic and reconstructive surgery. In theory, cells undergoing mesenchymal transition will achieve re-epithelialization through mesenchymal-epithelial transition at the end of wound healing. But in fact, some pathological stimuli will inhibit this biological process and result in scar formation. If mesenchymal-epithelial transition can be activated at the corresponding stage, the ideal wound healing may be accomplished. Two in vivo skin defect mouse models and dermal-derived mesenchymal cells were used to evaluate the effect of lithium chloride in wound healing. The mesenchymal-epithelial transition was detected by immunohistochemistry staining. In vivo, differentially expressed genes were analysed by transcriptome analyses and the subsequent testing was carried out. We found that lithium chloride could promote murine cutaneous wound healing and facilitate mesenchymal-epithelial transition in vivo and in vitro. In lithium chloride group, scar area was smaller and the collagen fibres are also orderly arranged. The genes related to mesenchyme were downregulated and epithelial mark genes were activated after intervention. Moreover, transcriptome analyses suggested that this effect might be related to the inhibition of CXCL9 and IGF2, subsequent assays demonstrated it. Lithium chloride can promote mesenchymal-epithelial transition via downregulating CXCL9 and IGF2 in murine cutaneous wound healing, the expression of IGF2 is regulated by ß-catenin. It may be a potential promising therapeutic drug for alleviating postoperative scar and promoting re-epithelialization in future.

Transcriptome heterogeneity of congenital cleft palate model in congener New Zealand rabbits induced by dexamethasone.

OBJECTIVES: This work aimed to investigate the transcriptome heterogeneity of dexamethasone-induced congenital cleft palate in homozygous New Zealand rabbits and determine the molecular mechanism underlying the occurrence of congenital cleft palate. METHODS: Dexamethasone (1.0 mg per day) was administered intramuscularly to 20 New Zealand pregnant rabbits from day 14 to day 17 of gestation, and the palatal phenotype of all offspring of each pregnant rabbit was observed. Eight embryos with a 4∶4 ratio of cleft palate to non-cleft palate were selected and divided into the cleft palate group (CP) and non-cleft palate group (NCP). Their palatal tissues were collected for RNA sequencing. RESULTS: A total of 225 differentially expressed genes (Q<0.05) were found in the CP group compared with the NCP group, of which 120 genes were upregulated and 105 genes were downregulated. The GO and KEGG enrichment analyses of these differentially expressed genes were carried out. The results showed significant enrichment in GO classification, which included heterotrimeric G protein complex, extracellular matrix, transcription factor complex, and basement membrane. Meanwhile, GABA ergic synapse, morphine addiction, retrograde endocannabinoid signaling, glutamate synapse, serotonergic synapse, regulation of actin cytoskeleton, and the Apelin signaling pathway were significantly enriched in the KEGG pathway. Compared with the NCP group, the gene expression levels of ARHGEF6 (P<0.05) and ABI2 (P<0.001) decreased in the CP group, and APC increased (P<0.001); these results were confirmed by real-time polymerase chain reaction. CONCLUSIONS: Abnormal expression levels of the ARHGEF6, APC, and ABI2 genes involved in the regulation of the actin cytoskeleton in the palatal synapse may be associated with the dexamethasone-induced congenital cleft palate in New Zealand rabbits.