Early Detection of Urinary Proteome Biomarkers for Effective Early Treatment of Pulmonary Fibrosis in a Rat Model

Wu, Jianhuang; Li, Xundou; Zhao, Mindi; Huang, He; Sun, Wei; Gao, Youhe

doi:10.1002/prca.201700103

Cited by 42 publications

(40 citation statements)

References 44 publications

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“…However, urine has been shown to provide clues for the early diagnosis of disease in a variety of animal models in our previous work. [34][35][36][37][38][39][40][41] The W256 breast carcinoma cell line has been used to construct a rat model of brain metastases that has a histopathology similar to that of patients with brain metastases. [42][43][44][45] Direct intracerebral injection of tumor cells can lead to tumor cell growth in the brain, which is the most well-controlled and reproducible method for establishing animal models of brain metastases.…”

Section: Discussionmentioning

confidence: 99%

Dynamic urinary proteomic analysis in a Walker 256 intracerebral tumor model

Zhang

Meng

et al. 2019

Cancer Medicine

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Background Patients with primary and metastatic brain cancer have an extremely poor prognosis, mostly due to the late diagnosis of disease. Urine, which lacks homeostatic mechanisms, is an ideal biomarker source that accumulates early and highly sensitive changes to provide information about the early stage of disease. Methods A rat model mimicking the local tumor growth process in the brain was established with intracerebral Walker 256 (W256) cell injection. Urine samples were collected on days 3, 5, and 8 after injection, and then analyzed by liquid chromatography coupled with tandem mass spectrometry. Results In the intracerebral W256 model, no obvious clinical manifestations or abnormal magnetic resonance imaging (MRI) signals were found on days 3 or 5; at these time points, 9 proteins were changed significantly in the urine of all eight tumor rats. On day 8, when tumors were detected by MRI, 25 differential proteins were identified, including 10 that have been reported to be closely related to brain metastasis or primary tumors. The differential urinary proteome was compared with those from the subcutaneous W256 model and the intracerebral C6 model. Few differential proteins overlapped, and specific differential protein patterns were observed among the three models. Conclusions These findings demonstrate that early changes in the urine proteome can be detected in the intracerebral W256 model. The urinary proteome can reflect the difference when tumor cells with different growth characteristics are inoculated into the brain and when identical tumor cells are inoculated into different areas, specifically, the subcutis and the brain.

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Section: Discussionmentioning

confidence: 99%

Dynamic urinary proteomic analysis in a Walker 256 intracerebral tumor model

Zhang

Meng

et al. 2019

Cancer Medicine

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“…For example, significant changes in urine occurred in a unilateral ureteral obstruction rat model, and urinary proteins showed continuous changes with disease progression in an adriamycin‐induced focal segmental glomerulosclerosis model . The urinary proteome changed significantly before clinical symptoms and histopathological changes occurred in a bleomycin‐induced pulmonary fibrosis model, an experimental autoimmune myocarditis model, a bacterial meningitis rat model, a glioblastoma animal model, and a Walker‐256 tumor‐bearing rat model …”

Section: Introductionmentioning

confidence: 99%

Urine Proteome Changes in a TNBS‐Induced Colitis Rat Model

Qin

Wang

et al. 2019

Proteomics Clinical Apps

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Purpose Urine is an important resource for biomarker research. Urine proteins reflect not only renal diseases but also changes in other organs in the body. However, urine has rarely been used to reflect on inflammatory bowel disease. Experimental Design In the present study, a trinitrobenzene sulfonic acid (TNBS)‐induced colitis rat model is used to mimic the human inflammatory bowel disease Crohn's disease (CD). Urine samples are analyzed by label‐free and TMT‐labeled proteomic quantitative methods. Results 77 urinary proteins are significantly changed in the colitis rats compared with that in the controls. These proteins are further validated by parallel reaction monitoring (PRM) targeted proteomic quantitative methods. Based on the human protein tissue atlas, carbonic anhydrase 1, ribonuclease pancreatic gamma type, and neutral and basic amino acid transport protein rBAT are highly enriched in the gastrointestinal tract. Among the nine PRM‐validated proteins, carbonic anhydrase 1, neutrophil collagenase, and neutrophil gelatinase associated lipocalin were previously reported as IBD‐associated proteins (all exhibiting consistent trends with the observation herein), whereas the others are newly discovered by this study. Conclusions and Clinical Relevance The results provide valuable clues for future study of urine biomarker of inflammatory bowel disease and Crohn's disease.

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“…In the model of focal segmental glomerulosclerosis induced by doxorubicin, the urinary proteins were continuously changing with disease progression [7]. There are other models of organ diseases as follows: bleomycin-induced pulmonary fibrosis model [8], experimental autoimmune myocarditis model [9], rat model of bacterial meningitis [10], glioblastoma animal model [11], tumor model of the subcutaneous implantation of Walker 256 cells [12], rat model of chronic pancreatitis induced by diethyldithiocarbamate [13], rat model of NuTu-19 lung metastasis [14], Walker 256 intracerebral tumor model [15], and Walker 256 lung metastasis rat model [16]. The urinary proteome changes significantly before the clinical signs and histopathological changes have occurred.…”

Section: Introductionmentioning

confidence: 99%

Early urine proteome changes in an implanted bone cancer rat model

Wang

Qin

et al. 2019

Preprint

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In this study, Walker 256 cells were implanted into rat tibiae. Urine samples were then collected on days 3, 5, 7, and 13 and were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). With label-free quantification, 25 proteins were found to change significantly in the urine of the tumor group mice compared with the proteins in the urine of the control group mice; this was even the case when there were no significant lesions identified in the Computed Tomography(CT) examination. Among these differentially proteins, 7 were reported to be associated with tumor bone metastasis. GO analysis shows that the differential proteins on day 3 were involved in several responses, including the acute phase response, the adaptive immune response and the innate immune response. The differentially proteins on day 7 were involved in the mineral absorption pathway. The differentially proteins on day 13 were involved in vitamin D binding and calcium ion binding. These processes may be associated with bone metastasis. Our results demonstrate that urine could sensitively reflect the changes in the early stage of implanted bone cancer; this provides valuable clues for future studies of urine biomarkers for tumor bone metastasis.

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Early Detection of Urinary Proteome Biomarkers for Effective Early Treatment of Pulmonary Fibrosis in a Rat Model

Abstract: Urinary proteomics has been underutilized in respiratory diseases. These findings will improve our understanding of the pathogenesis of PF and accelerate biomarker discovery in respiratory diseases.

Cited by 42 publications

References 44 publications

Dynamic urinary proteomic analysis in a Walker 256 intracerebral tumor model

Dynamic urinary proteomic analysis in a Walker 256 intracerebral tumor model

Urine Proteome Changes in a TNBS‐Induced Colitis Rat Model

Early urine proteome changes in an implanted bone cancer rat model

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