| Summary: | 博士 === 國防醫學院 === 生命科學研究所 === 97 === Ankyrin repeat domain 17 (Ankrd17) encodes an ubiquitously expressed protein with two clusters of ankyrin repeats. In order to elucidate its function(s), gene targeting strategy was used to ablate the Ankrd17 gene in mouse. The Ankrd17-deficient mice died between embryonic day (E) 10.5 and E11.5 due to cardiovascular defects. Serious hemorrhages were detected and the vascular smooth muscle cells (vSMCs) surrounding the vessels were drastically reduced in the Ankrd17-deficient embryos, suggesting that the vascular maturation was not completed. Interestingly, vSMC differentiation marker genes were up-regulated in the Ankrd17 mutant embryos. These genes were also up-regulated in a mouse vSMCs precursor cell line (C3H/10T1/2) when RNAi was applied to knockdown the Ankrd17 expression in these cells. Significantly, this up-regulation phenomenon was accompanied by a switch of the subcellular location of the Krüppel-like factor 4 (KLF4), a known repressor of the vSMC differentiation marker genes and an important player for the phenotype switching of vSMCs. Furthermore, 10T1/2 cells with knockdown of Ankrd17 expression exhibited reduced migration in a wound healing assay. These data together suggest that Ankrd17 participates in the maintenance of the dedifferentiation state of the vSMCs by restricting the expression of vSMC differentiation marker genes through control of the subcellular location of KLF4. Loss-of-function of Ankrd17 would then lead to the promiscuously high level of vSMC differentiation marker gene expression and consequently the defective migration of vSMCs from their originating sites to the vessel tubes.
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