Trefoil factor 2 (Tff2) deficiency in murine digestive tract influences the immune system

Background & Aims: The gastrointestinal trefoil factor family (TFF1, TFF2, TFF3) peptides are considered to play an important role in maintaining the integrity of the mucosa. The physiological role of TFF2 in the protection of the GI tract was investigated in TFF2 deficiency. Methods: TFF2-/- mice were generated and differential expression of various genes was assessed by using a mouse expression microarray, quantitative real time PCR, Northern blots or immunohistochemistry. Results: On an mRNA level we found 128 differentially expressed genes. We observed modulation of a number of crucial genes involved in innate and adaptive immunity in the TFF2-/- mice. Expression of proteasomal subunits genes (LMP2, LMP7 and PSMB5) involved in the MHC class I presentation pathway were modulated indicating the formation of immunoproteasomes improving antigen presentation. Expression of one subunit of a transporter (TAP1) responsible for importing degraded antigens into ER was increased, similarly to the BAG2 gene that modulates chaperone activity in ER helping proper loading on MHC class I molecules. Several mouse defensin (cryptdin) genes coding important intestinal microbicidal proteins were up-regulated as a consequence of TFF2 deficiency. Normally moderate expression of TFF3 was highly increased in stomach

ジゾクテキ キョクショ レーザー ショウシャ ト オンド カンジュセイ リポソーム ニ ヨル ミャクラクマク ジュンカン パターン ノ ヒョウカ

京都大学0048新制・課程博士博士(医学)甲第11383号医博第2806号新制||医||884(附属図書館)23026UT51-2005-D134京都大学大学院医学研究科外科系専攻(主査)教授 福山 秀直, 教授 富樫 かおり, 教授 橋本 信夫学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Finanční analýza Barum Continental spol. s r.o.

Cílem je zhodnotit finanční zdraví společnosti Barum Continental spol. s r.o. v letech 2001- 2005 na základě účetních výkazů. Práce je rozdělena na dvě části. V první, teoretické, blíže popisuji jednotlivé metody a základní principy, které jsou použity při konkrétních výpočtech v druhé části. Zde následuje také horizontální a vertikální rozbor účetních výkazů, bilanční pravidla, poměrová analýza (skupiny ukazatelů jako ukazatele rentability, likvidity, aktivity, zadluženosti), analýza pracovního kapitálu, Du Pontův rozklad, některé bankrotní a bonitní modely a nakonec mezipodnikové srovnání

コッカ ト ミブンセイ ギカイ : フランス コクセイシ ケンキュウ

京都大学0048新制・論文博士博士(法学)乙第11614号論法博第156号新制||法||118(附属図書館)23427UT51-2005-D532(主査)教授 林 信夫, 教授 大石 眞, 教授 小野 紀明学位規則第4条第2項該当Doctor of LawsKyoto UniversityDA

Identification of blottin: A novel gastric trefoil factor family-2 binding protein

The trefoil factor family (TFF) peptides are important in gastro-intestinal mucosal protection and repair. Their mechanism of action remains unclear and receptors are sought. We aimed to identify and characterise proteins binding to TFF2. A fusion protein of mouse TFF2 with alkaline phosphatase was generated and used to probe 2-D protein blots of mouse stomach. The resulting spots were analysed by MS. The protein identified was characterised by bioinformatics, rapid amplification of cDNA ends, in situ hybridisation (ISH) and immunohistochemistry (IHC). Functional assays were performed in gastrointestinal cell lines. A single major murine protein was identified and named blottin. It was previously unknown as a translated product. Blottin is also present in rat and human; the latter gene is also known as GDDR. The predicted full-length proteins are 184 amino acids long (20 kDa), reducing to 164 amino acids (18 kDa) after signal peptide cleavage. I S H of gastrointestinal tissues shows abundant blottin mRNA in gastric surface and foveolar epithelium. IHC shows cytoplasmic staining for blottin protein, and by immunoelectron microscopy in mucus granules and Golgi stacks. Previous work showed that blottin is down-regulated in gastric cancers. Blottin contains a BRICHOS domain, and has 56% similarity with gastrokine-1. Cultured HT-29 cells express blottin and show increased DNA synthesis with antiblottin antibody; however, this effect is reversed by the immunising peptide. We have identified and characterised a TFF2-binding protein produced by gastric epithelium. Blottin may play a role in gastrointestinal mucosal protection and modulate gut epithelial cell proliferation