Secretin stimulates biliary cell proliferation by regulating expression of microRNA 125b and microRNA let7a in mice.
Secretin stimulates biliary cell proliferation by regulating expression of microRNA 125b and microRNA let7a in mice.
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DOI：
10.1053/j.gastro.2014.02.030
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发表时间：
2014-06
期刊：
影响因子：
29.4
通讯作者：
Alpini G
中科院分区：
文献类型：
--
作者：
Glaser S;Meng F;Han Y;Onori P;Chow BK;Francis H;Venter J;McDaniel K;Marzioni M;Invernizzi P;Ueno Y;Lai JM;Huang L;Standeford H;Alvaro D;Gaudio E;Franchitto A;Alpini G
增殖的胆管细胞分泌和响应神经内分泌激素，包括分泌素。我们研究了S细胞和胆管细胞分泌的分泌素是否刺激小鼠胆道增殖。在分泌素敲除（Sct−/−）和野生型（对照）小鼠中，通过胆管结扎（BDL）诱导胆汁淤积。在BDL后第3天和第7天，对照小鼠和Sct - / -小鼠尾静脉注射抗microRNA 125b或let7a的morpholinos。1周后，收集肝组织和胆管细胞；免疫组化、免疫印迹、荧光素酶报告蛋白和实时荧光定量PCR检测。测量肝内胆管肿块（IBDM）和增殖。在条件培养基中测定胆管细胞、S细胞、血清和胆汁分泌分泌素。在对照组小鼠BDL后，胆管细胞和S细胞上清液以及血清和胆汁中分泌分泌素增加。与BDL对照组相比，BDL Sct - / -小鼠IBDM较低，增殖减少，血管内皮生长因子A （VEGFA）和神经生长因子（NGF）的产生减少。给予抗microRNA 125b或let7a的morpholinos的BDL和对照小鼠IBDM增加。给予抗microRNA 125b的morpholinos小鼠肝脏VEGFA表达增加，而给予抗microRNA let7a的morpholinos小鼠肝脏NGF表达增加。分泌素调节肝组织中VEGF和NGF的表达与microRNA 125b和let7a水平负相关。肝损伤后，胆管细胞和S细胞分泌的分泌素降低了microRNA 125b和let7a水平，导致VEGF和NGF上调。调节胆管细胞分泌素的表达可能是治疗胆道疾病的一种方法。
Proliferating cholangiocytes secrete and respond to neuroendocrine hormones including secretin. We investigated whether secretin secreted by S cells and cholangiocytes stimulates biliary proliferation in mice. Cholestasis was induced in secretin knockout (Sct−/−) and wild-type (control) mice by bile-duct ligation (BDL). At days 3 and 7 after BDL, control and Sct−/− mice received tail-vein injections of morpholinos against microRNA 125b or let7a. One week later, liver tissues and cholangiocytes were collected; immunohistochemical, immnoblot, luciferase reporter and real-time PCR assays were performed. Intrahepatic bile duct mass (IBDM) and proliferation were measured. Secretin secretion was measured in conditioned media from cholangiocytes and S cells, and in serum and bile. Secretin secretion was increased in supernatants from cholangiocytes and S cells and in serum and bile following BDL in control mice. BDL Sct−/− mice had lower IBDM, reduced proliferation, and reduced production of vascular endothelial growth factor A (VEGFA) and nerve growth factor (NGF) compared with BDL control. BDL and control mice given morpholinos against microRNA 125b or let7a had increased IBDM. Livers of mice given morpholinos against microRNA 125b had increased expression of VEGFA while those treated with morpholinos against microRNA let7a had increased expression of NGF. Secretin regulated VEGF and NGF expression that negatively correlated with microRNA 125b and let7a levels in liver tissue. Following liver injury, secretin produced by cholangiocytes and S cells reduces microRNA 125b and let7a levels, resulting in upregulation of VEGF and NGF. Modulation of cholangiocyte expression of secretin could be a therapeutic approach for biliary diseases.
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DOI：
10.1152/ajpgi.00118.2011
发表时间：
2011-10-01
影响因子：
4.5
作者：
Han, Yuyan;DeMorrow, Sharon;Alpini, Gianfranco
通讯作者：
Alpini, Gianfranco
影响因子：
13.5
作者：
Glaser, Shannon;Lam, Ian P.;Franchitto, Antonio;Gaudio, Eugenio;Onori, Paolo;Chow, Billy K.;Wise, Candace;Kopriva, Shelley;Venter, Julie;White, Mellanie;Ueno, Yoshiyuki;Dostal, David;Carpino, Guido;Mancinelli, Romina;Butler, Wendy;Chiasson, Valorie;DeMorrow, Sharon;Francis, Heather;Alpini, Gianfranco
通讯作者：
Alpini, Gianfranco
DOI：
10.1038/labinvest.2009.6
发表时间：
2009-04
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1152/ajpgi.1999.276.5.g1289
发表时间：
1999-05-01
影响因子：
4.5
作者：
LeSage, GD;Glaser, SS;Alpini, G
通讯作者：
Alpini, G
影响因子：
29.4
作者：
Alpini, G;Roberts, S;LaRusso, NF
通讯作者：
LaRusso, NF