title: T-2 Toxin Alters the Levels of Collagen II and Its Regulatory Enzymes MMPs/TIMP-1 in a Low-Selenium Rat Model of Kashin-Beck Disease.
abstract: The objectives of this study are to assess T-2 toxin's involvement in low selenium (Se)-induced Kashin-Beck disease (KBD) in rats and unveil the mechanisms underlying this disease. Two hundred thirty rats were randomly divided into two groups after weaning and fed normal or low-Se diets (n = 115), respectively, for a month. After low-Se model confirmation, rats in each group were subdivided into five: two subgroups (n = 20) were fed their current diets (normal or low-Se diets, respectively) for 30 and 90 days, respectively; two other subgroups (n = 25) received their current diets + low T-2 toxin (100 ng/g BW/day) for 30 and 90 days, respectively; and 25 rats were fed their current diets + high T-2 toxin (200 ng/g BW/day) for 30 days. Articular cartilage samples were extracted for hematoxylin and eosin (H&E) staining and immunohistochemistry. Western blot and reverse transcription-polymerase chain reaction (RT-PCR) were used to assess protein and mRNA levels, respectively, of collagen II, matrix metalloproteinase (MMP-1), MMP -3, MMP-13, and tissue inhibitor of metalloproteinase-1 (TIMP-1). Low Se and T-2 toxin synergistically affected animal fitness. Interestingly, low Se + T-2 toxin groups showed KBD characteristics. MMP-1, -3, and -13 mRNA and protein levels generally increased in low-Se groups, while collagen II and TIMP-1 levels showed a downward trend, compared with normal diet fed animals for the same treatment (P < 0.05). T-2 toxin's effect was dose but not time dependent. Low Se and T-2 toxin synergistically alter the expression levels of collagen II as well as its regulatory enzymes MMP-1, MMP-3, MMP-13, and TIMP-1, inducing cartilage damage. Therefore, T-2 toxin may cause KBD in low-Se conditions.
authors.affiliation: Department of Geriatric Surgery, The Second Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710004, China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Prevention and Health Care, The Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710004, China.
authors.forename: Haojie
authors.initials: H
authors.lastname: Yang
authors.affiliation: The Faculty of Science, Xi'an Jiao Tong University, Xi'an, Shaanxi Province, 710049, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Guan
authors.affiliation: Department of Clinical Nutrition, Xijing Hospital, The Fourth Military Medical University, Xian, 710032, China.
authors.forename: Senhai
authors.initials: S
authors.lastname: Xue
authors.affiliation: Institute of Endemic and Chronic Diseases Prevention, Center for Disease Control and Prevention, Zibo, Shandong Province, 255026, China.
authors.forename: Daiqin
authors.initials: D
authors.lastname: Song
authors.affiliation: Institute of Endemic Diseases, Xi'an Jiaotong University, College of Medicine, Xi'an, Shaanxi Province, 710061, China. chenjh0410@sina.com.
authors.forename: Jinghong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute of Endemic Diseases, Xi'an Jiaotong University, College of Medicine, Xi'an, Shaanxi Province, 710061, China. wzlun@mail.xjtu.edu.cn.
authors.forename: Zhilun
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism*; D004195:Disease Models, Animal; D006614:Hindlimb / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D057767:Kashin-Beck Disease / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012643:Selenium / Q000097:blood / Q000172:deficiency*; D013249:Sternum / Q000187:drug effects / Q000378:metabolism; D013605:T-2 Toxin / Q000633:toxicity*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*
chemical_list: D024043:Collagen Type II; C576839:TIMP1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases; D012643:Selenium; D013605:T-2 Toxin
keywords: Collagen II; Kashin-Beck disease; MMPs/TIMP-1; Rat model; T-2 toxin