کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9244153 | 1209903 | 2005 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Autophagic Cell Death of Pancreatic Acinar Cells in Serine Protease Inhibitor Kazal Type 3-Deficient Mice
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کلمات کلیدی
EGFGFPRT-PCRLC3SPINK1Pdx1TUNEL - تونلembryonic stem - ساقه جنینepidermal growth factor - عامل رشد اپیدرمیpolymerase chain reaction - واکنش زنجیره ای پلیمرازreverse-transcription polymerase chain reaction - واکنش زنجیره پلیمراز معکوس رونویسیPCR - واکنش زنجیرهٔ پلیمرازgreen fluorescent protein - پروتئین فلورسنت سبزmicrotubule-associated protein 1 light chain 3 - پروتئین مرتبط با میکروتوبول 1 زنجیره سبک 3
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Background & Aims: Serine protease inhibitor Kazal type 1 (SPINK1), which is structurally similar to epidermal growth factor, is thought to inhibit trypsin activity and to prevent pancreatitis. Point mutations in the SPINK1 gene seem to predispose humans to pancreatitis; however, the clinical significance of SPINK1 mutations remains controversial. This study aimed to elucidate the role of SPINK1. Methods: We generated Spink3-deficient (Spink3â/â) mice by gene targeting in mouse embryonic stem cells. Embryonic and neonatal pancreases were analyzed morphologically and molecularly. Specific probes were used to show the typical autophagy that occurs during acinar cell death. Results: In Spink3â/â mice, the pancreas developed normally up to 15.5 days after coitus. However, autophagic degeneration of acinar cells, but not ductal or islet cells, started from day 16.5 after coitus. Rapid onset of cell death occurred in the pancreas and duodenum within a few days after birth and resulted in death by 14.5 days after birth. There was limited inflammatory cell infiltration and no sign of apoptosis. At 7.5 days after birth, residual ductlike cells in the tubular complexes strongly expressed pancreatic duodenal homeodomain-containing protein 1, a marker of pancreatic stem cells, without any sign of acinar cell regeneration. Conclusions: The progressive disappearance of acinar cells in Spink3â/â mice was due to autophagic cell death and impaired regeneration. Thus, Spink3 has essential roles in the maintenance of integrity and regeneration of acinar cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 129, Issue 2, August 2005, Pages 696-705
Journal: Gastroenterology - Volume 129, Issue 2, August 2005, Pages 696-705
نویسندگان
Masaki Ohmuraya, Masahiko Hirota, Masatake Araki, Noboru Mizushima, Makoto Matsui, Takao Mizumoto, Kyoko Haruna, Shoen Kume, Motohiro Takeya, Michio Ogawa, Kimi Araki, Ken-ichi Yamamura,