Decreased CSTB, RAGE, and Axl Receptor Are Associated with Zika Infection in the Human Placenta
Zika virus (ZIKV) compromises placental integrity, infecting the fetus. However, the mechanisms associated with ZIKV penetration into the placenta leading to fetal infection are unknown. Cystatin B (CSTB), the receptor for advanced glycation end products (RAGE), and tyrosine-protein kinase receptor...
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MDPI AG
2022-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/22/3627 |
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| author | Gabriel Borges-Vélez Juan A. Arroyo Yadira M. Cantres-Rosario Ana Rodriguez de Jesus Abiel Roche-Lima Julio Rosado-Philippi Lester J. Rosario-Rodríguez María S. Correa-Rivas Maribel Campos-Rivera Loyda M. Meléndez |
| author_facet | Gabriel Borges-Vélez Juan A. Arroyo Yadira M. Cantres-Rosario Ana Rodriguez de Jesus Abiel Roche-Lima Julio Rosado-Philippi Lester J. Rosario-Rodríguez María S. Correa-Rivas Maribel Campos-Rivera Loyda M. Meléndez |
| author_sort | Gabriel Borges-Vélez |
| collection | DOAJ |
| description | Zika virus (ZIKV) compromises placental integrity, infecting the fetus. However, the mechanisms associated with ZIKV penetration into the placenta leading to fetal infection are unknown. Cystatin B (CSTB), the receptor for advanced glycation end products (RAGE), and tyrosine-protein kinase receptor UFO (AXL) have been implicated in ZIKV infection and inflammation. This work investigates CSTB, RAGE, and AXL receptor expression and activation pathways in ZIKV-infected placental tissues at term. The hypothesis is that there is overexpression of CSTB and increased inflammation affecting RAGE and AXL receptor expression in ZIKV-infected placentas. Pathological analyses of 22 placentas were performed to determine changes caused by ZIKV infection. Quantitative proteomics, immunofluorescence, and western blot were performed to analyze proteins and pathways affected by ZIKV infection in frozen placentas. The pathological analysis confirmed decreased size of capillaries, hyperplasia of Hofbauer cells, disruption in the trophoblast layer, cell agglutination, and ZIKV localization to the trophoblast layer. In addition, there was a significant decrease in CSTB, RAGE, and AXL expression and upregulation of caspase 1, tubulin beta, and heat shock protein 27. Modulation of these proteins and activation of inflammasome and pyroptosis pathways suggest targets for modulation of ZIKV infection in the placenta. |
| first_indexed | 2024-03-09T18:25:31Z |
| format | Article |
| id | doaj.art-8de32c3ba52348948485177d3113e7b3 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T18:25:31Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-8de32c3ba52348948485177d3113e7b32023-11-24T07:58:28ZengMDPI AGCells2073-44092022-11-011122362710.3390/cells11223627Decreased CSTB, RAGE, and Axl Receptor Are Associated with Zika Infection in the Human PlacentaGabriel Borges-Vélez0Juan A. Arroyo1Yadira M. Cantres-Rosario2Ana Rodriguez de Jesus3Abiel Roche-Lima4Julio Rosado-Philippi5Lester J. Rosario-Rodríguez6María S. Correa-Rivas7Maribel Campos-Rivera8Loyda M. Meléndez9Department of Microbiology and Medical Zoology, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USADepartment of Cell Biology and Physiology, College of Life Sciences, Brigham Young University, Provo, UT 84602, USAComprehensive Cancer Center, University of Puerto Rico, San Juan, PR 00936, USACenter for Collaborative Research in Health Disparities, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USACenter for Collaborative Research in Health Disparities, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USADepartment of Microbiology and Medical Zoology, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USADepartment of Microbiology and Medical Zoology, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USADepartment of Pathology and Laboratory Medicine, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USASchool of Dental Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USADepartment of Microbiology and Medical Zoology, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USAZika virus (ZIKV) compromises placental integrity, infecting the fetus. However, the mechanisms associated with ZIKV penetration into the placenta leading to fetal infection are unknown. Cystatin B (CSTB), the receptor for advanced glycation end products (RAGE), and tyrosine-protein kinase receptor UFO (AXL) have been implicated in ZIKV infection and inflammation. This work investigates CSTB, RAGE, and AXL receptor expression and activation pathways in ZIKV-infected placental tissues at term. The hypothesis is that there is overexpression of CSTB and increased inflammation affecting RAGE and AXL receptor expression in ZIKV-infected placentas. Pathological analyses of 22 placentas were performed to determine changes caused by ZIKV infection. Quantitative proteomics, immunofluorescence, and western blot were performed to analyze proteins and pathways affected by ZIKV infection in frozen placentas. The pathological analysis confirmed decreased size of capillaries, hyperplasia of Hofbauer cells, disruption in the trophoblast layer, cell agglutination, and ZIKV localization to the trophoblast layer. In addition, there was a significant decrease in CSTB, RAGE, and AXL expression and upregulation of caspase 1, tubulin beta, and heat shock protein 27. Modulation of these proteins and activation of inflammasome and pyroptosis pathways suggest targets for modulation of ZIKV infection in the placenta.https://www.mdpi.com/2073-4409/11/22/3627placentatrophoblastHofbauer cells (HC)Zika virus (ZIKV)tandem mass tagging (TMT) |
| spellingShingle | Gabriel Borges-Vélez Juan A. Arroyo Yadira M. Cantres-Rosario Ana Rodriguez de Jesus Abiel Roche-Lima Julio Rosado-Philippi Lester J. Rosario-Rodríguez María S. Correa-Rivas Maribel Campos-Rivera Loyda M. Meléndez Decreased CSTB, RAGE, and Axl Receptor Are Associated with Zika Infection in the Human Placenta Cells placenta trophoblast Hofbauer cells (HC) Zika virus (ZIKV) tandem mass tagging (TMT) |
| title | Decreased CSTB, RAGE, and Axl Receptor Are Associated with Zika Infection in the Human Placenta |
| title_full | Decreased CSTB, RAGE, and Axl Receptor Are Associated with Zika Infection in the Human Placenta |
| title_fullStr | Decreased CSTB, RAGE, and Axl Receptor Are Associated with Zika Infection in the Human Placenta |
| title_full_unstemmed | Decreased CSTB, RAGE, and Axl Receptor Are Associated with Zika Infection in the Human Placenta |
| title_short | Decreased CSTB, RAGE, and Axl Receptor Are Associated with Zika Infection in the Human Placenta |
| title_sort | decreased cstb rage and axl receptor are associated with zika infection in the human placenta |
| topic | placenta trophoblast Hofbauer cells (HC) Zika virus (ZIKV) tandem mass tagging (TMT) |
| url | https://www.mdpi.com/2073-4409/11/22/3627 |
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