Moreover, a study conducted by M?rker et al. placental CD14-positive macrophages and mesenchymal cells within the villous stroma were detected as PTPIP51 positive. Our data suggest that both proteins, PTPIP51 and PTP1B, play a role in differentiation and apoptosis of the cytotrophoblast and syncytiotrophoblast, respectively. Moreover, PTPIP51 may also serve as a cellular signaling partner in angiogenesis and vascular remodeling. (J Histochem Cytochem 57:143C153, 2009) gene is located on chromosome 15 (15q15.1) and encodes the corresponding full-length protein making up 470 amino acids by 12 exons. PTPIP51 is usually evolutionary conserved and was shown to be expressed in different mammalian tissues and organs (Stenzinger et al. 2005), cancer (Lv et al. 2006; Koch et al. in press), as well as different cell lines including BeWo cells (human choriocarcinoma cell line) (Stenzinger et al. 2005). A regulated layer-dependent expression pattern was particularly observed for epidermal and seminiferous epithelia, both requiring a carefully controlled balance between proliferation, differentiation, and apoptosis (Nickoloff and Denning 2001; Stenzinger et ML-323 al. 2005,2006). Moreover, a study conducted by M?rker et al. (2008) pointed to a crucial role for PTPIP51 during mouse vision development. In accordance with these data, Roger et al. (2007) described a stage-dependent, biphasic expression pattern of in postnatal retinal development, which is usually governed by ciliary neurotrophic factor (CNTF), a member of the interleukin-6 family that mediates its action by the Janus-kinase/signal transducers and activators of transcription (JAK-STAT) signaling pathways. ML-323 The protein was also found to be expressed during the embryonic development of other organs (M?rker D, unpublished data). Interestingly, ML-323 Lv et al. (2006) found the full-length form of PTPIP51 to harbor a mitochondrial target sequence, thereby enhancing apoptosis in vitro. Our own results on vitamin- and cytokine-regulated expression of PTPIP51 in a human keratinocyte cell line supported these results, and moreover, pointed to a role of PTPIP51 in the differentiation of cells (Stenzinger et al. 2006). As in the epidermis, the formation and functional integrity of the syncytiotrophoblast, evolving from the cytotrophoblast, Rabbit Polyclonal to HCFC1 essentially requires a finely tuned interplay between proliferation, differentiation, and apoptosis (Huppertz et al. 2006; Kar et al. 2007). The regulation of these processes is dependent on numerous signaling cascades, including tyrosine phosphorylation. Disturbances of this delicate balance ML-323 may lead to gestational trophoblastic diseases, such as moles and choriocarcinomas (Li et al. 2002; Shih 2007). For these reasons, we decided to study the histological localization of the novel protein PTPIP51 and its interacting partner PTP1B in human placenta during distinct weeks of gestation. Development of the placenta begins after implantation of the blastocyst with the decidual reaction and transformation of maternal endometrium. The placenta develops from the single cell layer (trophoblast) of the blastocyst, whereas the embryo evolves from the three to four cell layer region (embryoblast). The trophoblast undergoes rapid proliferation and differentiation into an inner cytotrophoblast and an outer syncytiotrophoblast. Undifferentiated cytotrophoblast cells invade maternal tissue and blood vessels of the decidua and myometrium. By terminal differentiation of mononucleated cytotrophoblast cells, the multinucleated syncytiotrophoblast arises. The syncytiotrophoblast forms an external layer without intercellular boundaries. Its cells form cords infiltrating the endometrium. Through the lytic activity of the syncytiotrophoblast, the maternal capillaries are eroded and anastomose with the trophoblast lacunae, which with progressing pregnancy form a single, connected system. Primary villi are formed by penetration of cytotrophoblast cells into the syncytiotrophoblast, which are invaded by the mesoblast. At the end of the third week, the villous mesoblast differentiates into connective tissue and blood vessels, which get connected to the embryonic blood vessels. The cytotrophoblast of the anchoring villi grows rapidly, forming the cytotrophoblast layers between the syncytiotrophoblast and ML-323 the uterine endometrium. After the fourth month, the cytotrophoblast slowly disappears from the walls of the placental villi, and the syncytiotrophoblast forms the only continuous layer separating the maternal blood and the fetal capillary endothelium. This study aims to further elucidate in vivo functional implications of PTPIP51.
