Comparison of Urinary Proteomes Among Three Animal Models
Biomarkers are the monitorable changes associated with physiological or pathological changes. Urine is not regulated by the homeostatic mechanism and can reflect multiple changes in the body. Animal models can simulate human disease processes, monitor disease changes, and provide clues for early diagnosis. In this chapter, clues are provided for the dominant model animals associated with disease selection by comparing the urine proteome of rats, guinea pigs, and golden hamsters. The peptides were cleaved by membrane digestion and analyzed by LC-MS/MS. The number of urine proteins in the three different animals was different, and also different in every system of the body. This provides a basis for selecting the best animal models for different diseases.
KeywordsUrine proteomics LC-MS/MS Animal model Rat Guinea pig Golden hamster
The most important finding for biomarkers is to look for detectable changes associated with physiological and pathophysiological processes (Gao 2013). Urine is not regulated by the homeostatic mechanism and can reflect changes in metabolism in the body, making it easy to collect. Therefore, urine is a good biological source for finding disease markers (Gao 2015).
However, human clinical urine samples are affected by a variety of physiological or pathological effects, such as age, gender, diet, exercise, and drugs (Wu and Gao 2015). Animal models are the most effective way to find the causal relationship between diseases for the following reasons: (1) using animal models to reduce the effects of genetic and environmental factors on urine proteomics; (2) helping to identify biomarkers at each stage, including early diagnosis; (3) because clinical patient care is unavoidable, animal models can avoid the effects of drugs on the proteome. Therefore, the use of animal models for the study of urine protein markers is more economical and controllable, which is conducive to early observation of diseases and monitoring of related pathophysiological changes during disease progression (Zhao et al. 2014).
In research activities, rats are commonly used to establish disease animal models and conduct proteomic research, such as rat kidney disease model (Carter et al. 2016; Rosner 2009), rat coronary artery disease model (Paapstel et al. 2016; Zimmerli et al. 2008; Mullen et al. 2011), and rat bladder cancer model (Zhu et al. 2016; Vrooman and Witjes 2008). However, rats are not the dominant model animals for all diseases. Different diseases should choose their corresponding dominant model animals. Therefore, it is more necessary to study the superior models and proteomes of other animals. The hamsters commonly used as experimental animals are mainly the golden hamster and the Chinese hamster. The golden hamster has 38 inbred lines, 17 mutant lines, and 38 distant crosses. The hamster is mainly used in biomedical research in oncology research, reproductive physiology and family planning research, vascular physiology and microcirculation research, nutrition research, and infectious disease research. The hamster is the main biological material for the study of rabies virus and Japanese encephalitis virus and its vaccine production (Cui et al. 2014). Guinea pigs, also known as the squirrel, are widely used in immunology, nutrition, physiology, toxicology, and infectious disease research.
In this chapter, we analyze the difference in urinary proteins between rats, golden hamsters, and guinea pigs to provide basic data for medical experiments and provide a basis for the selection of dominant animal models.
3.2 Results and Analysis
3.3 Research Prospects
At this stage, rats are commonly model animals, and reports of studies using guinea pigs and golden hamsters are rare. This study compared the urine proteins of rats, golden hamsters, and guinea pigs by proteomic methods in order to lay the data foundation for medical experiments and provide clues for the selection of dominant animal models.
In this study, the urine proteins of rats, guinea pigs, and golden hamsters were found to be very different. It can be seen from SDS-PAGE that the three kinds of animal have different high-abundance proteins and different abundance inhibition, and the protein expression of guinea pigs and golden hamsters is relatively similar. Therefore, the use of rats alone to establish disease animal models is not suitable for studying all diseases. The expression of urinary protein in rats, guinea pigs, and golden hamsters was different in each organ of every system, and the biological processes involved in them were also different. The expression of rats was the least. It indicated that golden hamsters and guinea pigs are relatively more dominant in the establishment of human disease models. For example, in our data, it can be seen that in the liver and pancreas, the expression of urinary protein in golden hamsters is high. Now in the medical field, the mortality of intrahepatic cholangiocarcinoma and pancreatic cancer is high, the early diagnosis is difficult, and the prognosis is poor. It is particularly important to look for urine protein markers for both diseases. By consulting the relevant literature, it has been reported that golden hamsters are dominant model animals for intrahepatic cholangiocarcinoma and pancreatic cancer (Kawaura et al. 2011; Takahashi et al. 2011). In the skin and lungs, although the urinary protein expression of guinea pigs is not as high as that of golden hamsters, the urine of golden hamsters is less and thicker. On the urine samples, guinea pigs are more suitable. The early diagnosis and differential diagnosis of skin allergies, skin blemishes, and chronic obstruction pulmonary disease are difficult, and the treatment is poor. Therefore, we can find the urine protein markers for differential diagnosis and monitor the disease progression and disease efficacy. It has been reported that the guinea pig is the dominant model of chronic obstructive pulmonary disease, skin irritation, skin dermatophytes, and other diseases (Basketter 2016; Cambier et al. 2017; Ramírez-Ramírez et al. 2017). Through the above research, the selection of disease animal models can be guided. For example, in the selection of liver and pancreatic disease models, we can give priority to golden hamsters. In disease models such as skin diseases, we can give priority to guinea pigs and combine the disease and animal characteristics and previous reports to correctly select the dominant model.
In summary, the use of guinea pigs, golden hamsters, and rats to select their corresponding disease models can improve the efficiency and accuracy of urine protein marker screening, and have more prospect in the search for urine protein markers for early diagnosis of human diseases.
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