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Nodal signals through activin receptor-like kinase 7 to inhibit trophoblast migration and invasion: implication in the pathogenesis of preeclampsia.
Am J Pathol 2011; 178(3):1177-89AJ

Abstract

Trophoblast cell invasion into the uterus is an essential process for successful pregnancy, and shallow invasion of trophoblasts into the maternal decidua is linked to preeclampsia. We have reported that Nodal, a member of the transforming growth factor-β superfamily, acts through activin receptor-like kinase 7 (ALK7) to inhibit trophoblast proliferation and to induce apoptosis. In this study, we examined the spatial and temporal expression patterns of Nodal and ALK7 in human placenta from normal and preeclamptic pregnancies and investigated whether Nodal regulated trophoblast migration and invasion. Nodal and ALK7 were detected in villous and extravillous trophoblast cell populations in early gestation, and their levels were strongly up-regulated in preeclamptic placenta. Overexpression of Nodal or constitutively active ALK7 decreased cell migration and invasion, whereas knockdown of Nodal and ALK7 had the opposite effects. In placental explant culture, treatment with Nodal inhibited trophoblast outgrowth, whereas Nodal small-interfering RNA strongly induced the expansion of explants and the migration of extravillous trophoblast cells. Nodal stimulated the secretion of tissue inhibitor of metalloproteinase-1 and inhibited matrix metalloproteinase (MMP)-2 and MMP-9 activity. These findings suggest that the Nodal/ALK7 pathway plays important roles in human placentation and that its abnormal signaling may contribute to the development of preeclampsia.

Authors+Show Affiliations

Department of Biology, York University, Toronto, Ontario, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21356369

Citation

Nadeem, Lubna, et al. "Nodal Signals Through Activin Receptor-like Kinase 7 to Inhibit Trophoblast Migration and Invasion: Implication in the Pathogenesis of Preeclampsia." The American Journal of Pathology, vol. 178, no. 3, 2011, pp. 1177-89.
Nadeem L, Munir S, Fu G, et al. Nodal signals through activin receptor-like kinase 7 to inhibit trophoblast migration and invasion: implication in the pathogenesis of preeclampsia. Am J Pathol. 2011;178(3):1177-89.
Nadeem, L., Munir, S., Fu, G., Dunk, C., Baczyk, D., Caniggia, I., ... Peng, C. (2011). Nodal signals through activin receptor-like kinase 7 to inhibit trophoblast migration and invasion: implication in the pathogenesis of preeclampsia. The American Journal of Pathology, 178(3), pp. 1177-89. doi:10.1016/j.ajpath.2010.11.066.
Nadeem L, et al. Nodal Signals Through Activin Receptor-like Kinase 7 to Inhibit Trophoblast Migration and Invasion: Implication in the Pathogenesis of Preeclampsia. Am J Pathol. 2011;178(3):1177-89. PubMed PMID: 21356369.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nodal signals through activin receptor-like kinase 7 to inhibit trophoblast migration and invasion: implication in the pathogenesis of preeclampsia. AU - Nadeem,Lubna, AU - Munir,Sadia, AU - Fu,Guodong, AU - Dunk,Caroline, AU - Baczyk,Dora, AU - Caniggia,Isabella, AU - Lye,Stephen, AU - Peng,Chun, PY - 2010/07/09/received PY - 2010/11/02/revised PY - 2010/11/18/accepted PY - 2011/3/2/entrez PY - 2011/3/2/pubmed PY - 2011/5/26/medline SP - 1177 EP - 89 JF - The American journal of pathology JO - Am. J. Pathol. VL - 178 IS - 3 N2 - Trophoblast cell invasion into the uterus is an essential process for successful pregnancy, and shallow invasion of trophoblasts into the maternal decidua is linked to preeclampsia. We have reported that Nodal, a member of the transforming growth factor-β superfamily, acts through activin receptor-like kinase 7 (ALK7) to inhibit trophoblast proliferation and to induce apoptosis. In this study, we examined the spatial and temporal expression patterns of Nodal and ALK7 in human placenta from normal and preeclamptic pregnancies and investigated whether Nodal regulated trophoblast migration and invasion. Nodal and ALK7 were detected in villous and extravillous trophoblast cell populations in early gestation, and their levels were strongly up-regulated in preeclamptic placenta. Overexpression of Nodal or constitutively active ALK7 decreased cell migration and invasion, whereas knockdown of Nodal and ALK7 had the opposite effects. In placental explant culture, treatment with Nodal inhibited trophoblast outgrowth, whereas Nodal small-interfering RNA strongly induced the expansion of explants and the migration of extravillous trophoblast cells. Nodal stimulated the secretion of tissue inhibitor of metalloproteinase-1 and inhibited matrix metalloproteinase (MMP)-2 and MMP-9 activity. These findings suggest that the Nodal/ALK7 pathway plays important roles in human placentation and that its abnormal signaling may contribute to the development of preeclampsia. SN - 1525-2191 UR - https://www.unboundmedicine.com/medline/citation/21356369/Nodal_signals_through_activin_receptor_like_kinase_7_to_inhibit_trophoblast_migration_and_invasion:_implication_in_the_pathogenesis_of_preeclampsia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9440(10)00203-8 DB - PRIME DP - Unbound Medicine ER -