Bmi1 is required for regeneration of the exocrine pancreas in mice.
Bmi1 is required for regeneration of the exocrine pancreas in mice.
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DOI：
10.1053/j.gastro.2012.05.009
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发表时间：
2012-09
期刊：
影响因子：
29.4
通讯作者：
Hebrok M
中科院分区：
文献类型：
--
作者：
Fukuda A;Morris JP 4th;Hebrok M
Bmi 1是Polycomb蛋白家族的成员，通过修饰特定启动子处的染色质组织来抑制转录。Bmi 1参与干细胞自我更新的控制，并已被证明可调节细胞增殖、组织稳态和分化。Bmi 1存在于自我更新的胰腺腺泡细胞亚群中，并在胰腺损伤时表达。我们研究了Bmi 1在外分泌胰腺再生中的作用。用雨蛙肽在Bmi 1 −/−小鼠中诱导急性胰腺炎;评估胰腺细胞再生、分化和凋亡。体外分析培养的Bmi 1 −/−和野生型原代腺泡，以确定Bmi 1缺失的腺泡特异性后果。为了研究Bmi 1在体内的细胞自主与非细胞自主作用，在用野生型造血系统重建的Bmi 1 −/−小鼠中诱导胰腺炎。在雨蛙素诱导的胰腺炎后再生过程中，胰腺外分泌部Bmi 1表达上调。对Bmi 1 −/−小鼠给予雨蛙肽后，外分泌再生受损。Bmi 1 −/−小鼠的胰腺发育不全，与野生型小鼠相比，外分泌胰腺被导管化生所取代，导管化生增加了细胞凋亡，减少了细胞增殖。损伤后，与野生型小鼠相比，Bmi 1 −/−胰腺中Cdkn 2a和p53依赖性凋亡基因的表达显著上调。此外，在将野生型小鼠的骨髓移植到Bmi 1 −/−小鼠后，嵌合体小鼠具有中等水平的胰腺发育不全和雨蛙素损伤后受损外分泌再生的显著但不完全的拯救。Bmi 1通过细胞自主机制（部分通过调节Cdkn 2a表达）和非细胞自主机制，在雨蛙素诱导的损伤后促进胰腺外分泌的再生。
Bmi1 is a member of the Polycomb protein family and represses transcription by modifying chromatin organization at specific promoters. Bmi1 is implicated in the control of stem cell self-renewal and has been shown to regulate cell proliferation, tissue homeostasis, and differentiation. Bmi1 is present in a subpopulation of self-renewing pancreatic acinar cells and is expressed in response to pancreatic damage. We investigated the role of Bmi1 in exocrine pancreas regeneration. Acute pancreatitis was induced in Bmi1−/− mice with caerulein; pancreatic cell regeneration, differentiation, and apoptosis were assessed. Cultured Bmi1−/− and wild-type primary acini were analyzed in vitro, to determine acinar-specific consequences of Bmi1 deletion. To investigate cell-autonomous vs non–cell-autonomous roles for Bmi1 in vivo, pancreatitis was induced in Bmi1−/− mice reconstituted with a wild-type hematopoietic system. Bmi1 expression was upregulated in the exocrine pancreas during regeneration after caerulein-induced pancreatitis. Exocrine regeneration was impaired following caerulein administration to Bmi1−/− mice. Pancreata of Bmi1−/− mice were hypoplastic, and the exocrine pancreas was replaced with ductal metaplasia that had increased apoptosis and decreased cell proliferation, compared to that of wild-type mice. Expression of Cdkn2a and p53-dependent apoptotic genes were markedly upregulated in Bmi1−/− pancreas, compared to wild-type mice, after injury. Furthermore, after transplantation of bone marrow from wild-type to Bmi1−/− mice, the chimeric mice had intermediate levels of pancreatic hypoplasia and significant, but incomplete, rescue of impaired exocrine regeneration after caerulein injury. Bmi1 contributes to regeneration of the exocrine pancreas after caerulein-induced injury through cell-autonomous mechanisms—in part by regulating Cdkn2a expression—and non-cell-autonomous mechanisms.
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影响因子：
29.4
作者：
Demols, A;Le Moine, O;Devière, J
通讯作者：
Devière, J
树突状细胞促进急性胰腺炎小鼠的胰腺生存力。
影响因子：
29.4
作者：
Bedrosian AS;Nguyen AH;Hackman M;Connolly MK;Malhotra A;Ibrahim J;Cieza-Rubio NE;Henning JR;Barilla R;Rehman A;Pachter HL;Medina-Zea MV;Cohen SM;Frey AB;Acehan D;Miller G
通讯作者：
Miller G
影响因子：
30.8
作者：
Kawaguchi, Y;Cooper, B;Wright, CVE
通讯作者：
Wright, CVE
DOI：
10.4161/cc.8.12.8744
发表时间：
2009-06-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
De La O JP;Murtaugh LC
通讯作者：
Murtaugh LC
影响因子：
50.3
作者：
Fukuda A;Wang SC;Morris JP 4th;Folias AE;Liou A;Kim GE;Akira S;Boucher KM;Firpo MA;Mulvihill SJ;Hebrok M
通讯作者：
Hebrok M