Tocharus Jiraporn, Tsuchiya Akiho, Kajikawa Miwa, Ueta Yoshifumi, Oka Chio, Kawaichi Masashi
Division of Gene Function in Animals, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0101, Japan.
Dev Growth Differ. 2004 Jun;46(3):257-74. doi: 10.1111/j.1440-169X.2004.00743.x.
The expression of mouse HtrA1 is developmentally regulated and restricted in embryo tissues which depend largely on TGF-beta signaling for their differentiation. We examined whether mouse HtrA3, another HtrA family member very close to HtrA1, shows similar expression patterns. HtrA3 and -1 were expressed mostly in the same embryonic organs but exhibited complementary patterns in various tissues; the lens epithelial cells in day 12.5 embryo expressed HtrA3 whereas the ciliary body and pigment retina expressed HtrA1. In the vertebrae of day 14.5 embryo, HtrA3 was expressed in the tail region, but HtrA1 was predominantly expressed in the thoracic and lumbar regions. Similar to HtrA1, HtrA3 bound to various TGF-beta proteins and inhibited the signaling of BMP-4, -2 and TGF-beta 1. HtrA3 did not inhibit signaling originated from a constitutively active BMP receptor, indicating that the inhibition occurred upstream of the cell surface receptor. HtrA3 also showed proteolytic activities indistinguishable from those of HtrA1 toward beta-casein and some extracellular matrix (ECM) proteoglycans. The protease activity was absolutely required for the TGF-beta signal inhibition activity. All these data suggest that HtrA3 and -1 have the overlapping biological activities but can function in complementary fashion in certain types of tissues.
小鼠HtrA1的表达受发育调控,且在胚胎组织中受到限制,这些胚胎组织的分化很大程度上依赖于TGF-β信号传导。我们研究了小鼠HtrA3(另一个与HtrA1非常接近的HtrA家族成员)是否表现出相似的表达模式。HtrA3和HtrA1大多在相同的胚胎器官中表达,但在不同组织中呈现互补模式;12.5天胚胎的晶状体上皮细胞表达HtrA3,而睫状体和色素视网膜表达HtrA1。在14.5天胚胎的椎骨中,HtrA3在尾部区域表达,但HtrA1主要在胸段和腰段区域表达。与HtrA1相似,HtrA3与多种TGF-β蛋白结合,并抑制BMP-4、-2和TGF-β1的信号传导。HtrA3不抑制源自组成型活性BMP受体的信号传导,这表明抑制发生在细胞表面受体的上游。HtrA3对β-酪蛋白和一些细胞外基质(ECM)蛋白聚糖也表现出与HtrA1难以区分的蛋白水解活性。蛋白酶活性对于TGF-β信号抑制活性是绝对必需的。所有这些数据表明,HtrA3和HtrA1具有重叠的生物学活性,但在某些类型的组织中可以以互补的方式发挥作用。