Smane-Filipova Liene, Pilmane Mara, Akota Ilze
Department of Morphology, Institute of Anatomy and Anthropology, Riga Stradins University, Dzirciema Street 16, Riga LV 1007, Latvia.
Institute of Stomatology, Riga Stradins University, Riga, Latvia.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016 Dec;160(4):538-542. doi: 10.5507/bp.2016.055. Epub 2016 Nov 21.
Morphogenesis of the upper lip and palate is a complex process involving highly regulated interactions between epithelial and mesenchymal cells. Genetic evidence in humans and mice indicates the involvement of matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) in cleft lip palate (CLP) aetiology. This study investigated whether expression of MMP-2, MMP-8, MMP-9, TIMP-2, and TIMP-4, which are essential for the upper lip and palate fusion, is dysregulated in children with CLP.
Oral mucosa tissue samples were obtained from patients with complete unilateral (CU) CLP (n = 25) and complete bilateral (CB) CLP (n = 19) during corrective plastic surgery and in unaffected control subjects (n = 10). MMPs and TIMPs expression was assessed by immunohistochemistry, and the data were analyzed using the Kruskal - Wallis test with the Bonferroni correction.
In CLP patients, MMP-2, TIMP-2 immunoreactivity in the oral mucosa was seen to have a few to abundant structures, but the overall number of MMP-2, TIMP-2-positive structures was greater than that in controls (P < 0.01). The total number of TIMP-4, MMP-9-positive cells showed a significant decrease in the CBCLP compared with that of CUCLP (P < 0.001). MMP-8 expression trends in the CLP group were similar to those of the control group.
The results suggest that TIMP-4 and MMP-9 are the main ECM remodeling regulatory proteins expressed in CUCLP affected tissues of the oral mucosa. The increased expression of MMP-2 and TIMP-2 in CLP tissues implicates these factors in the regulation of cell migration during ECM turnover independently of different types of clefts. Investigation of MMP and TIMP expression in tissue samples from patients with CLP appears to be a promising approach to the etiopathogenesis of CLP.
上唇和腭的形态发生是一个复杂的过程，涉及上皮细胞和间充质细胞之间高度调控的相互作用。人类和小鼠的遗传学证据表明基质金属蛋白酶（MMPs）及其内源性组织抑制剂（TIMPs）参与了唇腭裂（CLP）的病因学。本研究调查了对于上唇和腭融合至关重要的MMP-2、MMP-8、MMP-9、TIMP-2和TIMP-4在CLP患儿中表达是否失调。
在整形手术期间，从完全性单侧（CU）CLP患者（n = 25）、完全性双侧（CB）CLP患者（n = 19）以及未受影响的对照受试者（n = 10）获取口腔黏膜组织样本。通过免疫组织化学评估MMPs和TIMPs的表达，并使用经Bonferroni校正的Kruskal - Wallis检验分析数据。
在CLP患者中，口腔黏膜中MMP-2、TIMP-2免疫反应性可见少量至丰富的结构，但MMP-2、TIMP-2阳性结构的总数大于对照组（P < 0.01）。与CUCLP相比，CBCLP中TIMP-4、MMP-9阳性细胞总数显著减少（P < 0.001）。CLP组中MMP-8的表达趋势与对照组相似。
结果表明TIMP-4和MMP-9是在CUCLP口腔黏膜受影响组织中表达的主要细胞外基质重塑调节蛋白。CLP组织中MMP-2和TIMP-2表达增加表明这些因素在细胞外基质更新期间细胞迁移的调节中起作用，而与不同类型的腭裂无关。研究CLP患者组织样本中MMP和TIMP的表达似乎是了解CLP发病机制的一种有前景的方法。
