کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5860419 1133185 2014 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Osteopontin is an initial mediator of inflammation and liver injury during obstructive cholestasis after bile duct ligation in mice
ترجمه فارسی عنوان
استئوپنتین یک واسطه اولیه التهاب و آسیب کبدی در هنگام کلستازی انسداد پس از پیوند مجرای صفرا در موش است
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی


- Cholestatic liver injury occurs partially by neutrophil mediated hepatic necrosis.
- Osteopontin-deficient mice are protected against early cholestatic liver injury.
- Metalloproteinases cleave osteopontin to a pro-inflammatory form in bile.
- MMP inhibitor prevents neutrophil recruitment and early cholestatic liver injury.
- Osteopontin mediates neutrophil recruitment leading to cholestatic liver injury.

Osteopontin (OPN) is a chemotactic factor which can be cleaved to the pro-inflammatory form by matrix metalloproteinases (MMPs). To test the hypothesis that OPN can modulate inflammatory liver injury during cholestasis, wild-type (WT) C57BL/6 and OPN knockout (OPN-KO) mice underwent bile duct ligation (BDL). OPN-KO mice showed significant reduction in liver injury (plasma ALT and necrosis) and neutrophil recruitment compared with WT animals at 24 h but not 72 h after BDL. In WT mice, a 4-fold increase in hepatic MMP-3 mRNA and elevated MMP activities and cleaved OPN levels were observed in bile. WT mice subjected to BDL in the presence of the MMP inhibitor BB-94 showed reduced liver injury, less neutrophil extravasation and diminished levels of cleaved OPN in bile. Thus, during obstructive cholestasis, OPN released from biliary epithelial cells could be cleaved by MMPs in bile. When the biliary system leaks, cleaved OPN enters the parenchyma and attracts neutrophils. In the absence of OPN, other chemoattractants, e.g. chemokines, mediate a delayed inflammatory response and injury. Taken together, our data suggest that OPN is the pro-inflammatory mediator that initiates the early neutrophil-mediated injury phase during obstructive cholestasis in mice.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 224, Issue 2, 13 January 2014, Pages 186-195
نویسندگان
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