Fibroblast structure and function during regeneration from hormone-induced acute pancreatitis in the rat

The regeneration of the rat exocrine pancreas from a hormone-induced pancreatitis was investigated. In a previous study it was shown that the [3H]thymidine labeling index of interstitial cells increases 20- to 30-fold on day 1.5 after the induction of pancreatitis. Here we show by electron microscopic autoradiography that 80% of the labeled interstitial cells are fibroblasts. Their replication, fine structure, and collagen biosynthesis was further investigated: By day 2.5 numerous mitotic figures were found, indicating an enhanced proliferative activity of fibroblasts at the early stage of pancreatic regeneration. The ultrastructural analysis revealed that many fibroblasts contain abundant cytoplasm with a well-developed rough endoplasmic reticulum, prominent Golgi complexes, and secretory granules filled with fibrillar material. In contrast, the pancreatic fibroblasts of saline-infused control animals were shown to be spindle-shaped and to contain only very little cytoplasmic organelles. The collagen biosynthesis was quantified by in vivo labeling with [3H]proline and quantification of [3H]hydroxyproline in pancreatic protein hydrolysates. The collagen biosynthesis of experimental pancreata was measured to be 15 times that of controls on days 1.5 and 2.5 after the induction of pancreatitis and to remain fourfold elevated on days 3.5 through 10.5. In pulse-chase experiments using [3H]proline as the labeled precursor for collagen, the newly synthesized collagen was shown to be degraded with a half-life of 35 h. We conclude that replication of pancreatic fibroblasts and collagen biosynthesis as well as collagen degradation play important roles in the early phase of pancreatic regeneration.