Fibroblasts stimulate acinar cell proliferation through IGF-I during regeneration from acute pancreatitis
Fibroblasts stimulate acinar cell proliferation through IGF-I during regeneration from acute pancreatitis
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DOI：
10.1152/ajpgi.1999.276.1.g193
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发表时间：
1999-01-01
影响因子：
4.5
通讯作者：
Lutz, MP
中科院分区：
文献类型：
--
作者：
Ludwig, CU;Menke, A;Lutz, MP
雨蛙素诱导的胰腺炎后胰腺再生的特征是短暂的成纤维细胞增殖，随后是腺泡细胞的复制。协调再生的机制尚不完全清楚。在这项研究中，我们研究了胰岛素样生长因子 I (IGF-I) 的作用。雨蛙素输注12小时诱发大鼠急性水肿性胰腺炎。再生过程中，胰腺 IGF-I mRNA 水平增加了 50 倍以上，并在第 2 天达到最大值。免疫组织化学显示，IGF-I 定位于间质组织区域内的成纤维细胞。 IGF-I mRNA 在胰腺成纤维细胞的原代培养物中得到证实，但在培养的胰腺腺泡细胞中没有得到证实。然而，通过使用蛋白质印迹法，腺泡细胞确实表达了 IGF-I 受体。 IGF-I 刺激 5-溴-2'-脱氧尿苷摄取并以剂量依赖性方式增加腺泡细胞数量。刺激强度为 1.1 nM 时的最大刺激量的一半，并且被 IGF-I 拮抗剂和 IGF 结合蛋白 3 (IGFBP-3) 完全抑制。通过用成纤维细胞条件培养基刺激腺泡细胞增殖证实了可能的旁分泌调节，该增殖被IGF-I拮抗剂或IGFBP-3部分抑制。我们得出的结论是，胰腺炎晚期再生期间的腺泡细胞增殖至少部分是由成纤维细胞旁分泌释放 IGF-I 介导的。
Pancreatic regeneration after caerulein-induced pancreatitis is characterized by transient fibroblast proliferation followed by replication of acinar cells. The mechanisms that coordinate regeneration are incompletely understood. In this study, we examine the role of insulin-like growth factor I (IGF-I). Acute edematous pancreatitis was induced in rats by 12 h caerulein infusion. Pancreatic IGF-I mRNA levels increased over 50-fold during regeneration, reaching a maximum at day 2. Immunohistochemically, IGF-I was localized to fibroblasts within the areas of interstitial tissue. IGF-I mRNA was demonstrated in primary cultures of pancreatic fibroblasts but not in cultured pancreatic acinar cells. However, with the use of Western blotting acinar cells did express IGF-I receptors. IGF-I stimulated 5-bromo-2'-deoxyuridine uptake and increased numbers of acinar cells in a dose-dependent manner. Stimulation was half maximal at 1.1 nM and completely inhibited by an IGF-I antagonist and by IGF binding protein-3 (IGFBP-3). Possible paracrine regulation was confirmed by stimulation of acinar cell proliferation with fibroblast-conditioned medium, which was partially inhibited by IGF-I antagonist or by IGFBP-3. We conclude that acinar cell proliferation during late regeneration from pancreatitis is mediated at least in part by paracrine release of IGF-I from fibroblasts.