کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5509480 | 1400460 | 2016 | 43 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Repulsive guidance molecule b inhibits renal cyst development through the bone morphogenetic protein signaling pathway
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کلمات کلیدی
Dolichos biflorus agglutininSTSESRFDBAHGFMDCKRGMbADPKDPKDstaurosporine - استوسوسورپینkidney disease - بیماری کلیویautosomal dominant polycystic kidney disease - بیماری کلیوی پلی کیستیک غالب در اتواسوم غالب استHepatocyte growth factor - عامل رشد هپاتوسیتBMP - مدیریت فرایند کسب و کارEnd-stage renal failure - نارسایی کلیه در مرحله پایانیBone morphogenetic protein - پروتئین مورفوژنیک استخوانMadin-Darby canine kidney - کلیه های سگ کوچولو Madin-DarbyRenal cyst - کیست کلیه
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
Autosomal dominant polycystic kidney disease (ADPKD) is a monogenetic disease that still lacks effective therapy. Repulsive guidance molecule b (RGMb), a co-receptor for bone morphogenetic proteins (BMPs) and a ligand for neogenin, is expressed in renal tubular epithelial cells. Previous studies showed that RGMb plays negative roles in several types of tumors and prevents the immune system from over activation. The present study was designed to explore the effects of RGMb in ADPKD development. We found that expression of RGMb in kidney was less in PKD mice than wild-type mice. With stimulation of 8-bromo-cAMP, RGMb-null embryonic kidneys had greater cyst index, though their ureteric bud branched less than wild-type mice at E13.5. Postnatal RGMb-null kidneys showed interstitial hyperplasia and decreased tubular structures, especially in the boundary area of renal cortex and medulla. RGMb overexpression dramatically inhibited cyst development and promoted tubulogenesis in MDCK cells grown in 3D collagen gels. Biochemical analysis showed increased p-Smad1/5/8 and decreased p-ERK in RGMb-overexpressing MDCK cells, suggesting modulated BMP signaling. Specific inhibition of p-Smad1/5/8 by LDN193189 reversed the suppression of RGMb on MDCK cyst model. These results reveal RGMb as a novel regulator for ADPKD by promoting renal tubule branching and regulating BMP signaling pathway. Elevating RGMb and enhancing p-Smad1/5/8 are promising new strategies to treat ADPKD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 28, Issue 12, December 2016, Pages 1842-1851
Journal: Cellular Signalling - Volume 28, Issue 12, December 2016, Pages 1842-1851
نویسندگان
Jiangfeng Liu, Weiling Wang, Ming Liu, Limin Su, Hong Zhou, Yin Xia, Jianhua Ran, Herbert Y. Lin, Baoxue Yang,