PSP/reg inhibits cultured pancreatic stellate cell and regulates MMP/TIMP ratio
PSP/reg inhibits cultured pancreatic stellate cell and regulates MMP/TIMP ratio
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PSP/reg 抑制培养的胰腺星状细胞并调节 MMP/TIMP 比值
DOI：
10.1111/j.1365-2362.2010.02390.x
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发表时间：
2011-02-01
影响因子：
5.5
通讯作者：
Bachem, Max G.
中科院分区：
文献类型：
--
作者：
Li, Ling;Bimmler, Daniel;Bachem, Max G.
胰腺星状细胞（PSC）在急慢性胰腺炎的纤维化过程中起重要作用.胰腺结石蛋白/再生蛋白（PSP/reg）属于分泌应激蛋白（SSP）家族，由胰腺腺泡细胞组成性合成，在急性和慢性胰腺炎期间显著上调。假设这种应激蛋白的保护作用，我们研究了其对人PSC.Material and MethodsPancreatic星状细胞的影响，获得了从纤维化的人胰腺组织的副产物。PSP/reg在毕赤酵母中表达并从培养基上清液中纯化。将PSP/reg以100 ng/mL的浓度加入培养的PSC中。溴脱氧尿苷掺入法测定细胞增殖。通过伤口愈合测定评估PSC迁移。细胞外基质（I型胶原和纤维连接蛋白）、基质金属蛋白酶（MMPs）和基质金属蛋白酶组织抑制剂（TIMPs）在蛋白水平上被证实。可溶性胶原蛋白I和纤连蛋白减少后，加入PSP/注册。PSP/注册轻微降低MMP-1和MMP-2的合成，并强烈降低TIMP-1和TIMP-2浓度在PSC supernaturs.ConclusionsOur工作描述了一个新的方面，在体外PSP/注册降低PSC活性（增殖和迁移），并通过增加MMP/TIMP的比例刺激fibrolysis。提示PSP/reg可能通过促进纤维化的消退，在急慢性胰腺炎的修复阶段具有保护作用。我们强调PSP/reg作为胰腺损伤中的抗纤维化蛋白。
P>BackgroundPancreatic stellate cells (PSC) play a central role in fibrogenesis associated with acute and chronic pancreatitis. Pancreatic stone protein/regenerating protein (PSP/reg) belongs to a family of secretory stress proteins (SSP) that are constitutively synthesized by pancreatic acinar cells and upregulated dramatically during acute and chronic pancreatitis. Assuming a protective role of this stress protein, we investigated its effects on human PSC.Material and methodsPancreatic stellate cells were obtained by outgrowth from fibrotic human pancreas tissue. PSP/reg was expressed in the yeast Pichia pastoris and purified from medium supernatants. PSP/reg was added at concentrations of 100 ng/mL to cultured PSC. Cell proliferation was determined by bromodeoxyuridine incorporation. PSC migration was assessed by a wound healing assay. Extracellular matrix (collagen type I and fibronectin), matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) were demonstrated on protein level.ResultsPancreatic stone protein/regenerating protein inhibited PSC proliferation and migration. Soluble collagen I and fibronectin were reduced after the addition of PSP/reg. PSP/reg slightly decreased the synthesis of MMP-1 and MMP-2 and strongly decreased TIMP-1 and TIMP-2 concentrations in PSC supernatants.ConclusionsOur work describes a novel aspect that in vitro PSP/reg reduces PSC activity (proliferation and migration) and stimulates fibrolysis by increasing MMP/TIMP ratio. The findings suggest that PSP/reg might have a protective function in the repair phase of acute and chronic pancreatitis by promoting resolution of fibrosis. We highlight PSP/reg as an antifibrogenic protein in pancreatic injury.