Han Xiaonan, Sosnowska Danuta, Bonkowski Erin L, Denson Lee A
Cincinnati Children's Hospital Medical cetner and the University of Cincinnati College of Medicine, Ohio, USA.
Gastroenterology. 2005 Jul;129(1):185-203. doi: 10.1053/j.gastro.2005.05.018.
BACKGROUND & AIMS: Constitutive signal transducer and activator of transcription (STAT) 3 activation promotes chronic inflammation and epithelial proliferation in murine colitis and human inflammatory bowel disease. SHP-2, through binding to the glycoprotein 130 signaling receptor, negatively regulates STAT3 activation. Growth hormone reduces disease activity and promotes mucosal healing in colitis and can activate SHP-2.
We hypothesized that growth hormone administration would reduce disease activity in experimental colitis and that this would involve modulation of SHP-2/glycoprotein 130 association and STAT3 activation.
Growth hormone administration improved weight gain and colon histology in interleukin 10-null mice with colitis. Growth hormone reduced apoptosis and increased proliferation of crypt epithelial cells while increasing apoptosis of lamina propria mononuclear cells. Growth hormone increased SHP-2/glycoprotein 130 association and reduced colonic STAT3 activation in interleukin 10-null mice and in biopsy samples from patients with Crohn's colitis. Expression of the antiapoptotic protein bcl-2 was increased in crypt epithelial cells after growth hormone treatment. Growth hormone increased SHP-2/glycoprotein 130 binding and reduced interleukin 6-dependent STAT3 activation in the T84 human colon carcinoma and Jurkat human T-cell leukemia lines.
Growth hormone administration improves weight gain and reduces disease activity in interleukin 10-null mice with colitis. The improvement in disease activity is associated with increased SHP-2/glycoprotein 130 binding and reduced STAT3 activation in both murine and Crohn's colitis. Growth hormone may be a useful therapy in inflammatory bowel disease, in terms of both improving anabolic metabolism and enhancing mucosal healing.
组成型信号转导及转录激活因子（STAT）3激活可促进小鼠结肠炎和人类炎症性肠病中的慢性炎症及上皮细胞增殖。SHP-2通过与糖蛋白130信号受体结合，对STAT3激活起负向调节作用。生长激素可降低结肠炎的疾病活动度并促进黏膜愈合，且能激活SHP-2。
我们推测给予生长激素可降低实验性结肠炎的疾病活动度，且这一过程涉及对SHP-2/糖蛋白130结合及STAT3激活的调节。
给予生长激素可改善白细胞介素10基因敲除型结肠炎小鼠的体重增加及结肠组织学状况。生长激素减少了隐窝上皮细胞的凋亡并增加了其增殖，同时增加了固有层单核细胞的凋亡。生长激素增加了白细胞介素10基因敲除型小鼠及克罗恩结肠炎患者活检样本中SHP-2/糖蛋白130的结合，并降低了结肠STAT3的激活。生长激素治疗后，隐窝上皮细胞中抗凋亡蛋白bcl-2的表达增加。生长激素增加了T84人结肠癌细胞系和Jurkat人T细胞白血病细胞系中SHP-2/糖蛋白130的结合，并降低了白细胞介素6依赖性STAT3的激活。
给予生长激素可改善白细胞介素10基因敲除型结肠炎小鼠的体重增加并降低疾病活动度。疾病活动度的改善与小鼠和克罗恩结肠炎中SHP-2/糖蛋白130结合增加及STAT3激活降低有关。就改善合成代谢及促进黏膜愈合而言，生长激素可能是治疗炎症性肠病的一种有效疗法。
