期刊文献+

细胞外基质通过调节α3整合素的表达促进小鼠胰岛存活 被引量:1

Extraceilular matrix improves islet cell survival by α3-integrin regulation
原文传递
导出
摘要 目的确定重组基底膜提取物(BME)作为细胞外基质促进体外胰岛存活的分子通路。方法分离提纯小鼠胰岛并植入BME凝胶体外培养。蛋白印迹法检测Caspase-3,α1、α5整合素,胰岛功能相关蛋白PDX-1,信号传导相关蛋白Akt、FAK、Erk等的表达。结果研究显示BME可预防胰岛凋亡的发生。和未处理胰岛相比,胰岛植入BME后的Caspase-3表达水平下降和磷酸化Akt表达增加。此外,α3整合素的表达、FAK蛋白水平、磷酸化FAK的表达也显著提高。PDX-1和磷酸化Erk在培养48h时间点的表达显著增加,显示了BME对体外胰岛保存起到了正性调节的作用。结论胰岛体外BME包埋培养可以上调α3整合素及其下游信号转导,以提高其生存能力和胰岛细胞的功能。 Objective To determine the molecular pathway of reconstituted basement membrane extract (BME) embedment in the context of promoting islet cell survival. Methods Mouse islet cells were isolated and embedded in BME for in vitro culture. Caspase-3, integrin-α1 and 5, PDX-1, Akt, FAK and phospho Erk were detected using Western blot. Results Islet cells embedded with BME were partially protected from apoptosis indicated by a lower caspase-3 level and an increased phospho Akt activity compared with untreated control. In addition, an increase of α3-integrin, FAN protein level and FAK activity were observed as well. Furthermore, the expression of PDX-1 and phospho Erk at the 48 h mark were preserved, suggesting the positive effect of BME to islet activity. Conclusion These results indicate that the embedment of BME construction can up-regulate α3-integrin and its signal transduction, which may improve viability and function of islet cells.
出处 《中华肝胆外科杂志》 CAS CSCD 北大核心 2012年第3期220-225,共6页 Chinese Journal of Hepatobiliary Surgery
基金 基金项目:国家人事部优秀类回国启动基金(BJ2009-44) 北京市自然科学基金(5102039)
关键词 胰岛 α3整合素 细胞外基质 Pancreas islet α3-integrin Extracellular matrix
  • 相关文献

参考文献32

  • 1Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocor tieoid free immunosuppressive regimen [J]. N Engl J Med, 2000,343 : 230-238.
  • 2Croon AC, Karlsson R, Bergstrom C, et al. l.ack of donors limits the use of islet transplantation as treatment for diabetes [J]. Transplant Proc, 2003,35 : 764.
  • 3Paraskevas S, Maysinger D, Wang R, et al. Cell loss in isolated human islets occurs by apoptosis[J]. Pancreas, 2000,20: 270-276.
  • 4Marchetti P, Del Prato S, Lupi R, et al. The pancreatic beta cell in human type 2 diabetes[J]. Nutr Metab Cardiovasc Dis, 2006,16(Suppl 1) :3-6.
  • 5Nanji SA, Shapiro AM. Advances in pancreatic islet transplan tation in humans[J]. Diabetes Obes Metab, 2006,8: 15-25.
  • 6Pinkse GG, Bouwman WP, Jiawan Lalai R, et al. Integrin sig haling via RGD peptides and anti-betal antibodies confers re sistance to apoptosis in islets of Langerhans[J]. Diabetes, 2006,55:312-317.
  • 7Thomas FT, Contreras JL, Bilbao G, et al. Anoikis, extracel lular matrix, and apoptosis factors in isolated cell transplantation[J]. Surgery, 1999,126: 299-304.
  • 8Wang RN, Rosenberg L. Maintenance of beta-cell function and survival following islet isolation requires re establishment of the islet matrix relationship[J]. J Endocrinol, 1999,163: 181-190.
  • 9Kaido T, Yebra M, Cirulli V, et al. Regulation of human beta cell adhesion, motility, and insulin secretion by collagen Ⅳ and its receptor alphalbetal [J]. J Biol Chem, 2004, 279: 53762-53769.
  • 10Stendahl JC, Kaufman DB, Stupp SI. Extracellular matrix in pancreatic islets: relevance to scaffold design and transplantation[J]. Cell Transplant, 2009,18 : 1-12.

二级参考文献51

  • 1Shapiro AM,Ricordi C,Hering BJ,et al.International trial of the Edmonton protocol for islet transplantation.N Engl J Med,2006,355:1318-1330.
  • 2Alejandro R,Cutfield RG,Shienvold FL,et al.Natural history of intrahepatic canine islet cell autografts.J Clin Invest,1986,78:1339-1348.
  • 3Biarnes M,Montolio M,Nacher V,et al.Beta-cell death and mass in syngeneically transplanted islets exposed to short-and long-term hyperglycemia.Diabetes,2002,51:66-72.
  • 4Davalli AM,Ogawa Y,Ricordi C,et al.A selective decrease in the beta cell mass of human islets transplanted into diabetic nude mice.Transplantation,1995,59:817-820.
  • 5Ryan EA,Paty BW,Senior PA,et al.Five-year follow-up after clinical islet transplantation.Diabetes,2005,54:2060-2069.
  • 6Carlsson PO,Palm F,Andersson A,et al.Markedly decreased oxygen tension in transplanted rat pancreatic islets irrespective of the implantation site.Diabetes,2001,50:489-495.
  • 7Wang W,Upshaw L,Strong DM,et al.Increased oxygen consumption rates in response to high glucose detected by a novel oxygen biosensor system in non-human primate and human islets.J Endocrinol,2005,185:445-455.
  • 8Miao G,Ostrowski RP,Mace J,et al.Dynamic production of hypoxia-inducible factor-lalpha in early transplanted islets.Am J Transplant,2006,6:2636-2643.
  • 9Wang GL,Semenza GL.General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia.Proc Natl Acad Sci USA,1993,90:4304-4308.
  • 10Wang GL,Jiang BH,Rue EA,et al.Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.Proc Natl Acad Sci U S A,1995,92:5510-5514.

共引文献1

同被引文献11

  • 1Merani S,Toso C,Emamaullee J,et al.Optimal implantation site for pancreatic islet transplantation[J] .Br J Surg,2008,95 (12):1449-1461.
  • 2Barshes NR,Wyllie S,Goss JA.Inflammation-mediated dysfunction and apoptosis in pancreatic islet transplantation:implications for intrahepatic grafts[J] .J Leukoc Biol,2005,77 (5):587-597.
  • 3Caiazzo R,Gmyr V,Hubert T,et al.Evaluation of alternative sites for islet transplantation in the minipig:interest and limits of the gastric submucosa[J] .Transplant Proc,2007,39 (8):2620-2623.
  • 4Yin Z,Chen D,Hu F,et al.Cotransplantation with xenogenetic neonatal porcine sertoli cells significantly prolongs islet allograft survival in nonimmunosuppressive rats[J] .Transplantation,2009,88(3):339-345.
  • 5Pileggi A,Ricordi C,Alessiani M,et al.Factors influencing Islet of Langerhans graft function and monitoring[J] .Clin Chim Acta,2001,310(1):3-16.
  • 6Echeverri GJ,McGrath K,Bottino R,et al.Endoscopic gastric submucosal transplantation of islets (ENDO-STI):technique and initial results in diabetic pigs[J] .Am J Transplant,2009,9(11):2485-2496.
  • 7van der Windt D.J,Echeverri G J,Ijzermans JN,et al.The choice of anatomical site for islet transplantation[J] .Cell Transplant,2008,17(9):1005-1014.
  • 8Harlan DM,Kenyon NS,Korsgren O,et al.Current advances and travails in islet transplantation[J] .Diabetes,2009,58 (10):2175-2184.
  • 9宋京海,韦军民,陈剑,乔江春,朱明炜.胃黏膜下层胰岛移植物的生存率与功能的实验研究[J].中华肝胆外科杂志,2009,15(7):531-533. 被引量:2
  • 10江建新,孙诚谊.人工生物胰的体外分泌功能研究[J].中华肝胆外科杂志,2012,18(2):135-138. 被引量:1

引证文献1

二级引证文献2

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部