| Project/Area Number |
11671045
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Kidney internal medicine
|
|---|
| Research Institution | International University of Health and Welfare |
|---|
Principal Investigator |
HINOSHITA Fumihiko Associate Professor, Department of Health Science, International University of Health and Welfare, 保健学部, 助教授 (90260132)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ITOH Masahiko Associate Professor, Department of Health Science, International University of Health and Welfare, 保健学部, 助教授 (00245218)
橋本 尚詞 東京慈恵会医科大学, 医学部, 助教授
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
|---|
| Keywords | nivalenol / IgA nephropathy / small intestine / villi / goblet cell / electron microscopy / mucin / intra-intestinal injection / PAS染色 / IgA1抗体 / 小腸壁 |
|---|
| Research Abstract |
Based on the hypothesis that IgA nephropathy (IgAN) is triggered by some exogenous antigen (s) which induces dysregulation of the mucosal immune system, we have established a reproducible strain-nonspecific model of IgAN induced by oral administration of a mycotoxin, nivalenol (NIV). It was further confirmed that there are some immunological dysregulations in the gut-associated lymphoid tissue (GALT) of this IgAN model which might be associated with the pathogenesis of IgAN.
In the present study, intra-intestinal injection of NIV was carried out in mice to evaluate how NIV histopathologically influences the intestinal tract. After frequent practice, NIV 1 mg (50 mg/kg wt) or 0.2 mg (10 mg/kg wt) diluted in alcohol or saline phosphate buffer was injected into the duodenum in C3H/HeN mice. NIV-injected mice were sacrificed 24 or partly 6 hr later, and sections of the small intestine were examined by light micoscopy and compared with those in controls. Consequently, necrotic change and fus
… More
ion of the villi were observed in the proximal part of the small intestine close to the injection site. More interestingly, the number of PAS-positive goblet cells (GC) looked decreased even in the mid- and distal parts of the small intestine in the NIV-injected mice compared with those in controls. The numbers of PAS-positive GC in the cross sections of intestinal walls were precisely counted in a few groups with NIV, and statistically lower than those in controls. To confirm these findings, sections of the small intestine were further examined by electron micoscopy (EM). EM disclosed in the NIV-injected mice that GC largely disappeared and a greater part of the epithelial cells at the bases of villi and many Paneth cells near the crypts became necrotic and degenerated.
In conclusion, it was demonstrated that intra-intestinal NIV injected and then diluted in the small intestine decreases GC and induces necrosis and degeneration in epithelial cells and Paneth cells. These findings suggest that intra-intestinal NIV injection disturbs the proliferation of GC, epithelial cells and Paneth cells. The markedly decreased GC might diminish release of mucus granules (mucin) to protect against foreign antigens or hazards. This pathological change might cause dysregulation in GALT including Peyer's patch lymphocytes in the NIV-induced IgAN model. Less
|
