{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T22:25:00Z","timestamp":1781562300291,"version":"3.54.5"},"reference-count":55,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T00:00:00Z","timestamp":1644796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FIS-PI18\/00912"],"award-info":[{"award-number":["FIS-PI18\/00912"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Chronic venous disease (CVD) is a multifactorial vascular disorder frequently manifested in lower limbs in the form of varicose veins (VVs). Women are a vulnerable population for suffering from CVD, especially during pregnancy, when a plethora of changes occur in their cardiovascular system. Previous studies have indicated a worrisome association between CVD in pregnancy with the placental structure and function. Findings include an altered cellular behavior and extracellular matrix (ECM) composition. Integrin-linked kinase (ILK) is a critical molecule involved in multiple physiological and pathological conditions, and together with cadherins, is essential to mediate cell to ECM and cell to cell interplay, respectively. Thus, the aim of this study was to evaluate the implication of ILK and a set of cadherins (e-cadherin, cadherin-6 and cadherin-17) in placentas of women with CVD in order to unravel the possible pathophysiological role of these components. Gene expression (RT-qPCR) and protein expression (immunohistochemistry) studies were performed. Our results show a significant increase in the gene and protein expression of ILK, cadherin-6 and cadherin-17 and a decrease of e-cadherin in the placenta of women with CVD. Overall, this work shows that an abnormal expression of ILK, e-cadherin, cadherin-6 and cadherin-17 may be implicated in the pathological changes occurring in the placental tissue. Further studies should be conducted to determine the possible associations of these changes with maternal and fetal well-being.<\/jats:p>","DOI":"10.3390\/jpm12020277","type":"journal-article","created":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T03:46:00Z","timestamp":1644810360000},"page":"277","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Chronic Venous Disease in Pregnant Women Causes an Increase in ILK in the Placental Villi Associated with a Decrease in E-Cadherin"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2588-1708","authenticated-orcid":false,"given":"Miguel A.","family":"Ortega","sequence":"first","affiliation":[{"name":"Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Healthcare Research (IRYCIS), 28001 Madrid, Spain"},{"name":"Cancer Registry and Pathology Department, Hospital Universitario Principe de Asturias, 28801 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Chaowen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Fraile-Martinez","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Healthcare Research (IRYCIS), 28001 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cielo","family":"Garc\u00eda-Montero","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Healthcare Research (IRYCIS), 28001 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8389-258X","authenticated-orcid":false,"given":"Miguel A.","family":"Saez","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Healthcare Research (IRYCIS), 28001 Madrid, Spain"},{"name":"Pathological Anatomy Service, Central University Hospital of Defence-UAH, 28001 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Cruza","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Pereda-Cerquella","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel Angel","family":"Alvarez-Mon","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Healthcare Research (IRYCIS), 28001 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis G.","family":"Guijarro","sequence":"additional","affiliation":[{"name":"Ram\u00f3n y Cajal Institute of Healthcare Research (IRYCIS), 28001 Madrid, Spain"},{"name":"Unit of Biochemistry and Molecular Biology (CIBEREHD), Department of System Biology, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliia","family":"Fatych","sequence":"additional","affiliation":[{"name":"Unit of Biochemistry and Molecular Biology (CIBEREHD), Department of System Biology, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1238-190X","authenticated-orcid":false,"given":"C\u00e9sar","family":"Menor-Salv\u00e1n","sequence":"additional","affiliation":[{"name":"Unit of Biochemistry and Molecular Biology (CIBEREHD), Department of System Biology, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1309-7510","authenticated-orcid":false,"given":"Melchor","family":"Alvarez-Mon","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Healthcare Research (IRYCIS), 28001 Madrid, Spain"},{"name":"Immune System Diseases-Rheumatology and Oncology Service, University Hospital Pr\u00edncipe de Asturias, CIBEREHD, 28801 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6320-2668","authenticated-orcid":false,"given":"Juan","family":"De Leon-Luis","sequence":"additional","affiliation":[{"name":"Department of Public and Maternal and Child Health, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain"},{"name":"Department of Obstetrics and Gynecology, University Hospital Gregorio Mara\u00f1\u00f3n, 28009 Madrid, Spain"},{"name":"Health Research Institute Gregorio Mara\u00f1\u00f3n, 28009 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2419-2476","authenticated-orcid":false,"given":"Julia","family":"Buj\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Healthcare Research (IRYCIS), 28001 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0904-6198","authenticated-orcid":false,"given":"Natalio","family":"Garcia-Honduvilla","sequence":"additional","affiliation":[{"name":"Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"},{"name":"Ram\u00f3n y Cajal Institute of Healthcare Research (IRYCIS), 28001 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coral","family":"Bravo","sequence":"additional","affiliation":[{"name":"Department of Public and Maternal and Child Health, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain"},{"name":"Department of Obstetrics and Gynecology, University Hospital Gregorio Mara\u00f1\u00f3n, 28009 Madrid, Spain"},{"name":"Health Research Institute Gregorio Mara\u00f1\u00f3n, 28009 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7898-4685","authenticated-orcid":false,"given":"Angel","family":"As\u00fansolo-del-Barco","sequence":"additional","affiliation":[{"name":"Ram\u00f3n y Cajal Institute of Healthcare Research (IRYCIS), 28001 Madrid, Spain"},{"name":"Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcal\u00e1, 28801 Alcal\u00e1 de Henares, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.3904\/kjim.2018.230","article-title":"Chronic Venous Insufficiency and Varicose Veins of the Lower Extremities","volume":"34","author":"Youn","year":"2019","journal-title":"Korean J. Intern. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.bpobgyn.2013.08.001","article-title":"Alterations in Physiology and Anatomy during Pregnancy","volume":"27","author":"Tan","year":"2013","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"273","DOI":"10.4037\/aacnacc2018911","article-title":"Physiologic and Hemodynamic Changes During Pregnancy","volume":"29","author":"Troiano","year":"2018","journal-title":"AACN Adv. Crit. Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1161\/CIRCULATIONAHA.114.009029","article-title":"Cardiovascular Physiology of Pregnancy","volume":"130","author":"Sanghavi","year":"2014","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ortega, M.A., Fraile-Mart\u00ednez, O., Garc\u00eda-Montero, C., \u00c1lvarez-Mon, M.A., Chaowen, C., Ruiz-Grande, F., Pekarek, L., Monserrat, J., As\u00fansolo, A., and Garc\u00eda-Honduvilla, N. (2021). Understanding Chronic Venous Disease: A Critical Overview of Its Pathophysiology and Medical Management. J. Clin. Med., 10.","DOI":"10.3390\/jcm10153239"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"49","DOI":"10.5606\/tgkdc.dergisi.2019.16867","article-title":"Evaluation of quality of life after minimally invasive varicose vein treatment","volume":"27","year":"2019","journal-title":"Turk Gogus Kalp Damar Cerrahisi Derg."},{"key":"ref_7","first-page":"567","article-title":"Remodelling of Collagen Fibres in the Placentas of Women with Venous Insufficiency during Pregnancy","volume":"33","author":"Ortega","year":"2018","journal-title":"Histol. Histopathol."},{"key":"ref_8","first-page":"29","article-title":"Pregnancy and Lower Limb Varicose Veins: Prevalence and Risk Factors","volume":"9","author":"Del","year":"2010","journal-title":"J. Vasc. Bras."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1161\/CIRCRESAHA.118.313276","article-title":"Preeclampsia: Pathophysiology, Challenges, and Perspectives","volume":"124","author":"Rana","year":"2019","journal-title":"Circ. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1053\/plac.2002.0930","article-title":"Pre-Eclampsia, the Placenta and the Maternal Systemic Inflammatory Response\u2014A Review","volume":"24","author":"Redman","year":"2003","journal-title":"Placenta"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1136\/bmj.l2381","article-title":"Pre-Eclampsia: Pathophysiology and Clinical Implications","volume":"366","author":"Burton","year":"2019","journal-title":"BMJ"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1177\/1753944708097114","article-title":"Pre-Eclampsia: The Pivotal Role of the Placenta in Its Pathophysiology and Markers for Early Detection","volume":"3","author":"Hawfield","year":"2009","journal-title":"Ther. Adv. Cardiovasc. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.humpath.2018.03.022","article-title":"Placentas from Women with Pregnancy-Associated Venous Insufficiency Show Villi Damage with Evidence of Hypoxic Cellular Stress","volume":"77","author":"Ortega","year":"2018","journal-title":"Hum. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4157","DOI":"10.1111\/jcmm.15077","article-title":"Pregnancy-Associated Venous Insufficiency Course with Placental and Systemic Oxidative Stress","volume":"24","author":"Ortega","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ortega, M.A., Saez, M.A., Fraile-Mart\u00ednez, O., As\u00fansolo, \u00c1., Pekarek, L., Bravo, C., Coca, S., Sainz, F., \u00c1lvarez-Mon, M., and Buj\u00e1n, J. (2020). Increased Angiogenesis and Lymphangiogenesis in the Placental Villi of Women with Chronic Venous Disease during Pregnancy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072487"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/mmr.2021.12195","article-title":"An Increase in Elastogenic Components in the Placental Villi of Women with Chronic Venous Disease during Pregnancy Is Associated with Decreased EGFL7 Expression Level","volume":"24","author":"Ortega","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.7150\/ijms.58992","article-title":"Abnormal Proinflammatory and Stressor Environmental with Increased the Regulatory Cellular IGF-1\/PAPP-A\/STC and Wnt-1\/\u03b2-Catenin Canonical Pathway in Placenta of Women with Chronic Venous Disease during Pregnancy","volume":"18","author":"Ortega","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1083\/jcb.200108077","article-title":"Integrin-Linked Kinase (ILK) and Its Interactors: A New Paradigm for the Coupling of Extracellular Matrix to Actin Cytoskeleton and Signaling Complexes","volume":"155","author":"Wu","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1161\/01.RES.0000265233.40455.62","article-title":"Integrin-Linked Kinase at the Heart of Cardiac Contractility, Repair, and Disease","volume":"100","author":"Hannigan","year":"2007","journal-title":"Circ. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1095\/biolreprod.105.050419","article-title":"Integrin-Linked Kinase (ILK) Is Highly Expressed in First Trimester Human Chorionic Villi and Regulates Migration of a Human Cytotrophoblast-Derived Cell Line","volume":"74","author":"Elustondo","year":"2006","journal-title":"Biol. Reprod."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.gmit.2014.06.002","article-title":"Roles of Integrin-Linked Kinase in Cell Signaling and Its Perspectives as a Therapeutic Target","volume":"3","author":"Yen","year":"2014","journal-title":"Gynecol. Minim. Invasive Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3756","DOI":"10.1007\/s00018-008-8281-1","article-title":"The cell-cell adhesion molecule E-cadherin","volume":"65","author":"Berx","year":"2008","journal-title":"Cell Mol. Life Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s00418-005-0051-7","article-title":"E-Cadherin in the Assessment of Aberrant Placental Cytotrophoblast Turnover in Pregnancies Complicated by Pre-Eclampsia","volume":"124","author":"Brown","year":"2005","journal-title":"Histochem. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Casal, J.I., and Bartolom\u00e9, R.A. (2019). Beyond N-Cadherin, Relevance of Cadherins 5, 6 and 17 in Cancer Progression and Metastasis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133373"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.jvsv.2019.12.075","article-title":"The 2020 Update of the CEAP Classification System and Reporting Standards","volume":"8","author":"Lurie","year":"2020","journal-title":"J. Vasc. Surg. Venous Lymphat. Disord."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.7150\/ijms.54052","article-title":"Histopathological Study of JNK in Venous Wall of Patients with Chronic Venous Insufficiency Related to Osteogenesis Process","volume":"18","author":"Ortega","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","article-title":"The MIQE Guidelines: Minimum Information for Publication of Quantitative Real-Time PCR Experiments","volume":"55","author":"Bustin","year":"2009","journal-title":"Clin. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nprot.2006.83","article-title":"The Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate-Phenol-Chloroform Extraction: Twenty-Something Years On","volume":"1","author":"Chomczynski","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/1495170","article-title":"Implication of the PI3K\/Akt\/MTOR Pathway in the Process of Incompetent Valves in Patients with Chronic Venous Insufficiency and the Relationship with Aging","volume":"2018","author":"Ortega","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"226","DOI":"10.2144\/04372ST03","article-title":"AutoDimer: A Screening Tool for Primer-Dimer and Hairpin Structures","volume":"37","author":"Vallone","year":"2004","journal-title":"BioTechniques"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ye, J., Coulouris, G., Zaretskaya, I., Cutcutache, I., Rozen, S., and Madden, T.L. (2012). Primer-BLAST: A Tool to Design Target-Specific Primers for Polymerase Chain Reaction. BMC Bioinform., 13.","DOI":"10.1186\/1471-2105-13-134"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.5713\/ajas.20.0238","article-title":"TATA Box Binding Protein and Ribosomal Protein 4 Are Suitable Reference Genes for Normalization during Quantitative Polymerase Chain Reaction Study in Bovine Mesenchymal Stem Cells","volume":"33","author":"Jang","year":"2020","journal-title":"Asian-Australas. J. Anim. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1159\/000500449","article-title":"Unravelling the Role of Mapks (Erk1\/2) in Venous Reflux in Patients with Chronic Venous Disorder","volume":"206","author":"Ortega","year":"2019","journal-title":"Cells Tissues Organs"},{"key":"ref_34","first-page":"547","article-title":"Defective Expression of the Peroxisome Regulators PPAR\u03b1 Receptors and Lysogenesis with Increased Cellular Senescence in the Venous Wall of Chronic Venous Disorder","volume":"36","author":"Ortega","year":"2021","journal-title":"Histol. Histopathol."},{"key":"ref_35","first-page":"1","article-title":"Overexpression of IRS-4 Correlates with Procaspase 3 Levels in Tumoural Tissue of Patients with Colorectal Cancer","volume":"2018","author":"Guijarro","year":"2018","journal-title":"J. Oncol."},{"key":"ref_36","first-page":"959","article-title":"Human Skin Model for Mimic Dermal Studies in Pathology with a Clinical Implication in Pressure Ulcers","volume":"33","author":"Ortega","year":"2018","journal-title":"Histol. Histopathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.acthis.2013.11.001","article-title":"Overexpression of Integrin-Linked Kinase (ILK) Promotes Migration and Invasion of Colorectal Cancer Cells by Inducing Epithelial-Mesenchymal Transition via NF-\u039aB Signaling","volume":"116","author":"Yan","year":"2014","journal-title":"Acta Histochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1089\/dna.2013.2229","article-title":"Ultrasound Microbubble-Mediated Delivery of Integrin-Linked Kinase Gene Improves Endothelial Progenitor Cells Dysfunction in Pre-Eclampsia","volume":"33","author":"Cui","year":"2014","journal-title":"DNA Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1210\/en.2014-1643","article-title":"Gestational Diabetes Alters Offspring DNA Methylation Profiles in Human and Rat: Identification of Key Pathways Involved in Endocrine System Disorders, Insulin Signaling, Diabetes Signaling, and ILK Signaling","volume":"156","author":"Petropoulos","year":"2015","journal-title":"Endocrinology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4589","DOI":"10.1242\/jcs.112.24.4589","article-title":"Integrin-Linked Kinase Is Localized to Cell-Matrix Focal Adhesions but Not Cell-Cell Adhesion Sites and the Focal Adhesion Localization of Integrin-Linked Kinase Is Regulated by the PINCH-Binding ANK Repeats","volume":"112","author":"Li","year":"1999","journal-title":"J. Cell Sci."},{"key":"ref_41","first-page":"4099","article-title":"The Role of Integrin-Linked Kinase in the Molecular Architecture of Focal Adhesions","volume":"126","author":"Elad","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1523\/JNEUROSCI.2113-16.2016","article-title":"Integrin-Linked Kinase (ILK) Deletion Disrupts Oligodendrocyte Development by Altering Cell Cycle","volume":"37","author":"Hussain","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"13937","DOI":"10.1074\/jbc.272.21.13937","article-title":"Overexpression of the Integrin-Linked Kinase Promotes Anchorage-Independent Cell Cycle Progression","volume":"272","author":"Radeva","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3154","DOI":"10.1038\/sj.onc.1208525","article-title":"ILK Mediates Actin Filament Rearrangements and Cell Migration and Invasion through PI3K\/Akt\/Rac1 Signaling","volume":"24","author":"Qian","year":"2005","journal-title":"Oncogene"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/S0955-0674(99)00083-6","article-title":"Cell-Substrate Interactions and Signaling through ILK","volume":"12","author":"Dedhar","year":"2000","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4813","DOI":"10.1091\/mbc.e03-05-0308","article-title":"Integration of Cell Attachment, Cytoskeletal Localization, and Signaling by Integrin-Linked Kinase (ILK), CH-ILKBP, and the Tumor Suppressor PTEN","volume":"14","author":"Attwell","year":"2003","journal-title":"Mol. Biol. Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5444","DOI":"10.1038\/sj.onc.1203928","article-title":"The Integrin Linked Kinase (ILK) Induces an Invasive Phenotype via AP-1 Transcription Factor-Dependent Upregulation of Matrix Metalloproteinase 9 (MMP-9)","volume":"19","author":"Troussard","year":"2000","journal-title":"Oncogene"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.placenta.2010.06.017","article-title":"Cadherins in the Human Placenta\u2014Epithelial-Mesenchymal Transition (EMT) and Placental Development","volume":"31","author":"Kokkinos","year":"2010","journal-title":"Placenta"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"126","DOI":"10.3109\/14767058.2014.989203","article-title":"Trophoblastic E-Cadherin and TGF-Beta Expression in Placenta Percreta and Normal Pregnancies","volume":"29","author":"Incebiyik","year":"2016","journal-title":"J. Matern.-Fetal Neonatal Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.placenta.2015.04.001","article-title":"The Invasive Phenotype of Placenta Accreta Extravillous Trophoblasts Associates with Loss of E-Cadherin","volume":"36","author":"Duzyj","year":"2015","journal-title":"Placenta"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1097\/00004347-200301000-00013","article-title":"Expression of E-Cadherin and Beta-Catenin in Trophoblastic Tissue in Normal and Pathological Pregnancies","volume":"22","author":"Li","year":"2003","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1002\/dvdy.21685","article-title":"Integrin-Linked Kinase Regulates E-Cadherin Expression through PARP-1","volume":"237","author":"McPhee","year":"2008","journal-title":"Dev. Dyn."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12958-020-00624-w","article-title":"Characterization of the role for cadherin 6 in the regulation of human endometrial receptivity","volume":"18","author":"Zhou","year":"2020","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1111\/j.1600-0897.1998.tb00341.x","article-title":"Type 2 cadherins in the human endometrium and placenta: Their putative roles in human implantation and placentation","volume":"39","author":"MacCalman","year":"1998","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1097\/PAP.0000000000000008","article-title":"Cadherin 17 is a novel diagnostic marker for adenocarcinomas of the digestive system","volume":"21","year":"2014","journal-title":"Adv. Anat. Pathol."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/2\/277\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:19:00Z","timestamp":1760134740000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/2\/277"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,14]]},"references-count":55,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["jpm12020277"],"URL":"https:\/\/doi.org\/10.3390\/jpm12020277","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,14]]}}}