Transcriptional profiling of the bladder in urogenital schistosomiasis reveals pathways of inflammatory fibrosis and urothelial compromise
| العنوان: | Transcriptional profiling of the bladder in urogenital schistosomiasis reveals pathways of inflammatory fibrosis and urothelial compromise |
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| المؤلفون: | Tyrrell A. Nelson, Shailja Patel, Debalina Ray, Justin I. Odegaard, Chi Ling Fu, Michael H. Hsieh, Diana N. Gong |
| المصدر: | PLoS Neglected Tropical Diseases, Vol 6, Iss 11, p e1912 (2012) PLoS Neglected Tropical Diseases |
| بيانات النشر: | Public Library of Science (PLoS), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Pathology, Mouse, RC955-962, Pathogenesis, medicine.disease_cause, Global Health, urologic and male genital diseases, Mice, Schistosomiasis haematobia, 0302 clinical medicine, Molecular cell biology, Fibrosis, Arctic medicine. Tropical medicine, Schistosomiasis, Schistosoma haematobium, 0303 health sciences, Mice, Inbred BALB C, Urinary bladder, Bladder Cancer and Urothelial Neoplasias of the Urinary Tract, biology, Systems Biology, Bladder and Ureteric Disorders, Animal Models, 3. Good health, Host-Pathogen Interaction, medicine.anatomical_structure, Infectious Diseases, 030220 oncology & carcinogenesis, Medicine, Female, Public aspects of medicine, RA1-1270, Research Article, Neglected Tropical Diseases, medicine.medical_specialty, Urology, Immunology, DNA transcription, Urinary Bladder, Microbiology, Host-Parasite Interactions, Urothelial Hyperplasia, 03 medical and health sciences, Model Organisms, medicine, Parasitic Diseases, Animals, Claudin, Biology, Immunity to Infections, 030304 developmental biology, Urologic Infections, Microarray analysis techniques, Gene Expression Profiling, Public Health, Environmental and Occupational Health, Immunity, biology.organism_classification, medicine.disease, Microarray Analysis, Gene expression profiling, Disease Models, Animal, Parasitology, Gene expression, Carcinogenesis |
| الوصف: | Urogenital schistosomiasis, chronic infection by Schistosoma haematobium, affects 112 million people worldwide. S. haematobium worm oviposition in the bladder wall leads to granulomatous inflammation, fibrosis, and egg expulsion into the urine. Despite the global impact of urogenital schistosomiasis, basic understanding of the associated pathologic mechanisms has been incomplete due to the lack of suitable animal models. We leveraged our recently developed mouse model of urogenital schistosomiasis to perform the first-ever profiling of the early molecular events that occur in the bladder in response to the introduction of S. haematobium eggs. Microarray analysis of bladders revealed rapid, differential transcription of large numbers of genes, peaking three weeks post-egg administration. Many differentially transcribed genes were related to the canonical Type 2 anti-schistosomal immune response, as reflected by the development of egg-based bladder granulomata. Numerous collagen and metalloproteinase genes were differentially transcribed over time, revealing complex remodeling and fibrosis of the bladder that was confirmed by Masson's Trichrome staining. Multiple genes implicated in carcinogenesis pathways, including vascular endothelial growth factor-, oncogene-, and mammary tumor-related genes, were differentially transcribed in egg-injected bladders. Surprisingly, junctional adhesion molecule, claudin and uroplakin genes, key components for maintaining the urothelial barrier, were globally suppressed after bladder exposure to eggs. This occurred in the setting of urothelial hyperplasia and egg shedding in urine. Thus, S. haematobium egg expulsion is associated with intricate modulation of the urothelial barrier on the cellular and molecular level. Taken together, our findings have important implications for understanding host-parasite interactions and carcinogenesis in urogenital schistosomiasis, and may provide clues for novel therapeutic strategies. Author Summary Parasitic Schistosoma haematobium worms cause urogenital schistosomiasis in 112 million people worldwide. These worms lay eggs in the bladder wall, resulting in inflammation, fibrosis (internal scarring), bladder cancer, and passage of eggs into the urine. Indeed, the International Agency for Research on Cancer within the World Health Organization has classified S. haematobium as a “Class I” agent (“Carcinogenic to humans”). Moreover, S. haematobium-induced fibrosis and resulting obstructive kidney failure leads to 150,000 deaths annually. As a result, S. haematobium infection is one of the most important causes of worm-related death globally. In spite of this, research on this parasite is sparse due to a lack of suitable animal models. We have used our recently developed mouse model of urogenital schistosomiasis to understand the global bladder gene response to this infection. Large numbers of genes featured differential transcription after experimental infection, including specific immune response-, fibrosis-, cancer-, and bladder function-related genes. The relevance of these gene-based findings was verified through microscopic examination of egg-exposed bladders. Our data will improve our comprehension of urogenital schistosomiasis, and may help identify new targets for diagnosis and treatment of this disease, and possibly bladder cancer and bladder-based inflammatory disorders as well. |
| اللغة: | English |
| تدمد: | 1935-2735 1935-2727 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ab6f1a9b712eba23e9de52db2c838508 https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23209855/pdf/?tool=EBI |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ab6f1a9b712eba23e9de52db2c838508 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19352735 19352727 |
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