OBJECTIVES: To investigate regulation of microRNA (miR)-200 family (a, b, c, 141, and 429) in chronic pancreatitis (CP). This was accomplished by examining miR-200 family levels in a mouse model in vivo and their regulation in pancreatic cells in vitro. METHODS: Chronic pancreatitis was induced by cerulein for 4 weeks (50 μg/kg, 5 hourly intraperitoneal injections/day, and 3 days/week). Control mice received normal saline. The pancreata were harvested for fibrosis assessment by Sirius red staining and for miRNA, collagen, and fibronectin levels by quantitative PCR. In vitro, human primary pancreatic stellate cells and human primary pancreatic fibroblast (hPFBs), and rat pancreatic epithelial AR42J cells were treated with vehicle, transforming growth factor (TGF)-β (1 ng/mL), or BMP2 (50 ng/mL) for 24 hours and then harvested for miRNA analysis. RESULTS: In CP, miR-200s were decreased by 56% to 70% and inversely correlated with pancreatic fibrosis, miR-21, and miR-31 (P < 0.05). In vitro, TGF-β inhibited miR-200b in AR42J cells by 62%, whereas BMP2 increased miR-200b in all 3 cell types in a range of 1.5- to 3.4-fold and inhibited miR-21 in hPFBs by 21% (P < 0.05). CONCLUSIONS: Both in vivo and in vitro studies suggest an antifibrogenic function of miR-200s in CP. The TGF-β and BMP2 may function through inverse regulation of miR-200b levels.
OBJECTIVES: To investigate regulation of microRNA (miR)-200 family (a, b, c, 141, and 429) in chronic pancreatitis (CP). This was accomplished by examining miR-200 family levels in a mouse model in vivo and their regulation in pancreatic cells in vitro. METHODS:Chronic pancreatitis was induced by cerulein for 4 weeks (50 μg/kg, 5 hourly intraperitoneal injections/day, and 3 days/week). Control mice received normal saline. The pancreata were harvested for fibrosis assessment by Sirius red staining and for miRNA, collagen, and fibronectin levels by quantitative PCR. In vitro, human primary pancreatic stellate cells and human primary pancreatic fibroblast (hPFBs), and ratpancreatic epithelial AR42J cells were treated with vehicle, transforming growth factor (TGF)-β (1 ng/mL), or BMP2 (50 ng/mL) for 24 hours and then harvested for miRNA analysis. RESULTS: In CP, miR-200s were decreased by 56% to 70% and inversely correlated with pancreatic fibrosis, miR-21, and miR-31 (P < 0.05). In vitro, TGF-β inhibited miR-200b in AR42J cells by 62%, whereas BMP2 increased miR-200b in all 3 cell types in a range of 1.5- to 3.4-fold and inhibited miR-21 in hPFBs by 21% (P < 0.05). CONCLUSIONS: Both in vivo and in vitro studies suggest an antifibrogenic function of miR-200s in CP. The TGF-β and BMP2 may function through inverse regulation of miR-200b levels.
Authors: Fanny Wai-Tsing Shek; Robert Christopher Benyon; Fiona Mairi Walker; Peter Raymond McCrudden; Sylvia Lin Foon Pender; Elizabeth Jean Williams; Penelope Ann Johnson; Colin David Johnson; Adrian Calvin Bateman; David Roger Fine; John Peter Iredale Journal: Am J Pathol Date: 2002-05 Impact factor: 4.307
Authors: Shanzhong Yang; Sami Banerjee; Andressa de Freitas; Yan Y Sanders; Qiang Ding; Sadis Matalon; Victor J Thannickal; Edward Abraham; Gang Liu Journal: Am J Pathol Date: 2011-12-20 Impact factor: 4.307
Authors: R Perdigão-Henriques; F Petrocca; G Altschuler; M P Thomas; M T N Le; S M Tan; W Hide; J Lieberman Journal: Oncogene Date: 2015-03-23 Impact factor: 9.867