Ishihara T, Hayasaka A, Yamaguchi T, Kondo F, Saisho H
First Department of Medicine, Chiba University School of Medicine, Japan.
Pancreas. 1998 Nov;17(4):412-8. doi: 10.1097/00006676-199811000-00013.
Little is known about the pathogenesis of fibrosis in chronic pancreatitis. To reach a better understanding of this problem, we investigated the immunolocalizations of type IV collagen (Col-IV) and laminin around pancreatic ducts, and those of matrix metalloproteinase-2,9 (MMP-2,9), tissue inhibitors of metalloproteinase-1,2), and transforming growth factor-beta 1 (TGF beta 1) at the ductal epithelia in chronic pancreatitis. This study included 20 surgical specimens of fibrotic pancreas from patients with chronic pancreatitis and five normal samples from autopsy cases. Immunostaining was performed by the streptavidin-biotin method after antigen retrieval. We evaluated the staining patterns and the percentage of positive cells of each antigen. In chronic pancreatitis, the immunostainings of Col-IV and laminin along the basement membrane (BM) of pancreatic ducts were disrupted in 11 (55%) of 20 and eight (40%) of 20, respectively, whereas no disruption was detected in normal pancreas. Positive immunostainings for MMP-2, MMP-9, TIMP-1, and TIMF-2 in ductal epithelia were 15 (75%) of 20, five (25%) of 20, four (20%) of 20, and 10 (50%) of 20, respectively, whereas no immunostaining was seen in normal pancreas. The staining intensity of MMP-2 in ductal epithelia was associated with the staining intensity of Col-IV around the pancreatic ducts. Also, the staining intensity of MMP-2 was progressively increased in proportion to the staining intensity of TGF beta 1. These findings suggest that TGF beta 1 induced in pancreatic duct cells also induced MMP-2 in an autocrine or paracrine manner, and that this MMP-2 decomposed Col-IV of the BM of pancreatic ducts in chronic pancreatitis.
关于慢性胰腺炎中纤维化的发病机制，人们了解甚少。为了更好地理解这个问题，我们研究了慢性胰腺炎中胰管周围IV型胶原（Col-IV）和层粘连蛋白的免疫定位，以及基质金属蛋白酶-2、9（MMP-2、9）、金属蛋白酶组织抑制剂-1、2（TIMP-1、2）和转化生长因子-β1（TGF-β1）在导管上皮的免疫定位。本研究包括20例慢性胰腺炎患者纤维化胰腺的手术标本和5例尸检病例的正常样本。抗原修复后，采用链霉亲和素-生物素法进行免疫染色。我们评估了每种抗原的染色模式和阳性细胞百分比。在慢性胰腺炎中，20例中有11例（55%）和20例中有8例（40%）胰管基底膜（BM）上的Col-IV和层粘连蛋白免疫染色被破坏，而正常胰腺中未检测到破坏。导管上皮中MMP-2、MMP-9、TIMP-1和TIMP-2的阳性免疫染色分别为20例中的15例（75%）、20例中的5例（25%）、20例中的4例（20%）和20例中的10例（50%），而正常胰腺中未见免疫染色。导管上皮中MMP-2的染色强度与胰管周围Col-IV的染色强度相关。此外，MMP-2的染色强度与TGF-β1的染色强度成比例地逐渐增加。这些发现表明，胰腺导管细胞中诱导的TGF-β1也以自分泌或旁分泌方式诱导MMP-2，并且这种MMP-2在慢性胰腺炎中分解了胰管BM的Col-IV。
