Pigs, Unlike Mice, Have Two Distinct Colonic Stem Cell Populations Similar to Humans That Respond to High-Calorie Diet prior to Insulin Resistance
| Autor: | Sung Woo Kim, Lavanya Reddivari, Rob Knight, Venkata Charepalli, Frank Shen, Vadiraja B. Bhat, Sridhar Radhakrishnan, Jairam Vanamala, Matam Vijay-Kumar, Xia Xiao, Elisabeth Eriksson, Qiang Li |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Cancer Research medicine.medical_specialty Colorectal cancer Colon Swine medicine.medical_treatment Crypt Clinical Sciences Oncology and Carcinogenesis Biology Article Oral and gastrointestinal 03 medical and health sciences Mice Random Allocation 0302 clinical medicine Insulin resistance Downregulation and upregulation Internal medicine medicine Animals Humans Oncology & Carcinogenesis Intestinal Mucosa Cancer Nutrition Insulin Stem Cells medicine.disease Stem Cell Research Diet Colo-Rectal Cancer 030104 developmental biology Endocrinology Oncology 030220 oncology & carcinogenesis Immunology Stem cell Insulin Resistance Digestive Diseases Dysbiosis Homeostasis |
| Zdroj: | Cancer prevention research (Philadelphia, Pa.), vol 10, iss 8 |
| Popis: | Basal colonic crypt stem cells are long lived and play a role in colon homeostasis. Previous evidence has shown that high-calorie diet (HCD) enhances colonic stem cell numbers and expansion of the proliferative zone, an important biomarker for colon cancer. However, it is not clear how HCD drives dysregulation of colon stem cell/colonocyte proliferative kinetics. We used a human-relevant pig model and developed an immunofluorescence technique to detect and quantify colonic stem cells. Pigs (n = 8/group) were provided either standard diet (SD; 5% fat) or HCD (23% fat) for 13 weeks. HCD- and SD-consuming pigs had similar total calorie intake, serum iron, insulin, and glucose levels. However, HCD elevated both colonic proliferative zone (KI-67) and stem cell zone (ASCL-2 and BMI-1). Proliferative zone correlated with elevated innate colonic inflammatory markers TLR-4, NF-κB, IL6, and lipocalin-2 (r ≥ 0.62, P = 0.02). Elevated gut bacterial phyla proteobacteria and firmicutes in HCD-consuming pigs correlated with proliferative and stem cell zone. Colonic proteome data revealed the upregulation of proteins involved in cell migration and proliferation and correlated with proliferative and stem cell zone expansion. Our study suggests that pig colon, unlike mice, has two distinct stem cells (ASCL-2 and BMI-1) similar to humans, and HCD increases expansion of colonic proliferative and stem cell zone. Thus, pig model can aid in the development of preventive strategies against gut bacterial dysbiosis and inflammation-promoted diseases, such as colon cancer. Cancer Prev Res; 10(8); 442–50. ©2017 AACR. |
| Databáze: | OpenAIRE |
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