Skip to main content
Log in

Morphological identification of and collagen synthesis by periacinar fibroblastoid cells cultured from isolated rat pancreatic acini

  • Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Rat pancreatic periacinar fibroblastoid cells (PFCs) appear to be involved in intralobular fibrosis and acinar cell regeneration. We isolated pancreatic acini of the rat, cultured the fibroblastoid cells, and characterized the cells morphologically and immunohistochemically. Isolated acini were seeded on culture dishes, and spindle-shaped cells migrated and proliferated. On Electronmicroscopic examination, microfilament bundles were seen, and the intracellular localization of vimentin, α-smooth muscle actin, and non-muscle myosin was identified immunohistochemically. These findings strongly suggest that the cells were myofibroblast-like. The PFCs were also demonstrated, immunohistochemically, to contain prolyl hydroxylase, type-I procollagen, type-III procollagen, type-IV collagen, fibronectin, and laminin. Stimulation by transforming growth factor β1 (TGF β1) increased intracellular immunoreactive prolyl hydroxylase and collagen synthesis in the PFCs. These findings indicate that PFCs proliferate in culture as myofibroblast-like cells and synthesize extracellular matrix components. It is possible that PFCs are involved in intralobular fibrosis in response to stimulation with TGF β1.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Buck CA, Horwitz AF. Cell surface receptors for extracellular matrix molecules. Ann Rev Cell Biol 1987;3:179–205.

    CAS  PubMed  Google Scholar 

  2. Ekblom P, Vestweber D, Kemler R. Cell-matrix interactions and cell adhesion during development. Ann Rev Cell Biol 1986;2:1–26.

    Google Scholar 

  3. Shintani Y, Bamba T, Inoue H, et al. Effect of reconstituted basement membrane on growth and secretory function in pancreatic acinar AR42J cells. J Gastroenterol 1993;28:393–400.

    CAS  Google Scholar 

  4. Darby I, Skalli O, Gabbiani G. α-Smooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing. Lab Invest 1990;63:21–29.

    CAS  PubMed  Google Scholar 

  5. Kennedy RH, Bockman DE, Uscanga L, et al. Pancreatic extracellular matrix alterations in chronic pancreatitis. Pancreas 1987;2(1):61–72.

    Article  CAS  PubMed  Google Scholar 

  6. Kurkinen M, Vaheri A, Roberts PJ, et al. Sequential appearance of fibronectin and collagen in experimental granulation tissue. Lab Invest 1980;43:47–51.

    CAS  PubMed  Google Scholar 

  7. Martinez HA. The hepatic extracellular matrix II. Electron immunohistochemical studies in rats with CCl4-induced cirrhosis. Lab Invest 1985;53(2):166–186.

    Google Scholar 

  8. Vaheri A, Kurkinen M, Lehto VP, et al. Codistribution of pericellular matrix proteins in cultured fibroblasts and loss in transformation: Fibronectin and procollagen. Proc Natl Acad Sci USA 1978:75:4944.

    CAS  PubMed  Google Scholar 

  9. Elsasser HP, Adler G, Kern HF. Fibroblast structure and function during regeneration from hormone-induced acute pancreatitis in the rat. Pancreas 1989;4:169–178.

    CAS  PubMed  Google Scholar 

  10. Walker NI, Winterford CM, Kerr JFR. Ultrastructure of the rat pancreas after experimental duct ligation. II. Duct and stromal cell proliferation, differentiation, and deletion. Pancreas 1992; 7:420–434.

    Article  CAS  PubMed  Google Scholar 

  11. Morohoshi T, Kanda M. Periacinar fibroblastoid cell: Its action in early stage of alcoholic pancreatitis (in Japanese). Tan to Sui (J Bil Tract Pancreas) 1985;6(9):1205–1211.

    Google Scholar 

  12. Naguro T, Iino A. Three-dimensional features of pancreatic cells. In: Riva A, Motta PM (eds) Ultrastructure of the extraparietal glands of the digestive trace. Kluwer Academic, 1990;147–175.

  13. Casini A, Pinzani M, Milani S, et al. Regulation of extracellular matrix synthesis by transforming growth factor β1 in human fatstoring cells. Gastroenterology 1993;105:245–253.

    CAS  PubMed  Google Scholar 

  14. Duncan MR, Berman B. Differential regulation of collagen, glycosaminoglycan, fibronectin and collagenase activity production in cultured human adult dermal fibroblasts by interleukin 1 alpha and beta and tumor necrosis factor alpha and beta. J Invest Dermatol 1989;92(5):699–706.

    Article  CAS  PubMed  Google Scholar 

  15. Williams JA, Kore M, Dormer RL. Action of secretagogues on a new preparation of functionally intact, isolated pancreatic acini. Am J Physiol 1978:E517–E524.

  16. Kawaguchi Y, Kitani A, Hara M, et al. Cytokine regulation of prolyl 4-hydroxylase production in skin fibroblast cultures from patients with systemic sclerosis: Contribution to collagen synthesis and fibrosis. J Rheumatol 1992;19:1195–1201.

    CAS  PubMed  Google Scholar 

  17. Gabbiani G, Hirschel BJ, Ryan GB. Granulation tissue as a contractile organ. J Exp Med 1972;135:719–734.

    Article  CAS  PubMed  Google Scholar 

  18. Gabbiani G, Kapanci Y, Barazzone P, et al. Immunochemical indentification of intermediate-sized filaments in human neoplastic cells. A diagnostic aid for the surgical pathologist. Am J Pathol 1981;104:206–216.

    CAS  PubMed  Google Scholar 

  19. Skalli O, Ropraz P, Trzaciak A, et al. A monoclonal antibody against α-smooth muscle actin: A new probe for smooth muscle differentiation. J Cell Biol 1986;103(6):2787–2796.

    Article  CAS  PubMed  Google Scholar 

  20. Rockey DC, Boles JK, Gabbiani G, et al. Rat hepatic lipocytes express smooth muscle actin upon activation in vivo and in culture. J Submicrosc Cytol Pathol 1992;24(2):193–203.

    CAS  PubMed  Google Scholar 

  21. Fujiwara K, Pollard TD. Fluorescent antibody localization of myosin in the cytoplasm, cleavage furrow, and mitotic spindle of human cells. J Cell Biol 1976;71:848–875.

    Article  CAS  PubMed  Google Scholar 

  22. Larson DM, Fujiwara K, Alexander RW, et al. Heterogeneity of myosin antigenic expression in vascular smooth muscle in vivo. Lab Invest 1984;50(4):401–407.

    CAS  PubMed  Google Scholar 

  23. Robert JE, Jane AP, James JT. Evidence for the non-muscle nature of the myofibroblast of granulation tissue and hypertrophic scar. Am J Pathol 1988;130:252–260.

    Google Scholar 

  24. Buoro S, Ferrarese P, Chiavegato A, et al. Myofibroblast-derived smooth muscle cells during remodelling of rabbit urinary bladder wall induced by partial outflow obstruction. Lab Invest 1993; 69(5):589–602.

    CAS  PubMed  Google Scholar 

  25. Oda D, Grown AM, Vande Berg JS, et al. The fibroblast-like nature of myofibroblasts. Exp Mol Pathol 1988;49:316–329.

    Article  CAS  PubMed  Google Scholar 

  26. Nouchi T, Tanaka Y, Tukada T, et al. Appearance of α-smooth muscle actin-positive cells in hepatic fibrosis. Liver 1991;11:100–105.

    CAS  PubMed  Google Scholar 

  27. Vyalov SL, Gabbiani K, Kapanci Y. Rat alveolar myofibroblasts acquire α-smooth muscle actin expression during bleomycin-induced pulmonary fibrosis. Am J Pathol 1993;143(6):1754–1765.

    CAS  PubMed  Google Scholar 

  28. Zhang K, Rekhter MD, Gordon D, et al. Myofibroblasts and their role in lung collagen gene expression during pulmonary fibrosis. A combined immunohistochemical and in situ hybridization study. Am J Pathol 1994;145(1):114–125.

    CAS  PubMed  Google Scholar 

  29. Tsukamoto H, Tower SJ, French SW. Potentiation of ethanol-induced pancreatic injury by dietary fat. Induction of chronic pancreatitis by alcohol in rats. Am J Pathol 1988;131(2):246–257.

    CAS  PubMed  Google Scholar 

  30. Tanaka T, Ichiba Y, Fuji Y, et al. New canine model of chronic pancreatitis due to chronic ischemia with incomplete pancreatic duct obstruction. Digestion 1988;41:149–155.

    CAS  PubMed  Google Scholar 

  31. Onizuka S, Ito M, Sekine I, et al. Spontaneous pancreatitis in spontaneously hypertensive rats. Pancreas 1994;9:54–61.

    Article  CAS  PubMed  Google Scholar 

  32. Mori Y, Yokoyama J, Nishimura M, et al. Diabetic strain (WBN/Kob) of rat characterized by endocrine-exocrine pancreatic impairment due to distinct fibrosis. Pancreas 1990;5:452–459.

    Article  CAS  PubMed  Google Scholar 

  33. Suda K, Aki J, Nakamura T. Pancreatic fibrosis in patients with alcoholic dependent syndreme. Arch Pathol Lab Med 1993; 117:1013–1016.

    CAS  PubMed  Google Scholar 

  34. Friedman SL. The cellular basis of hepatic fibrosis. N Engl J Med 1993;328:1828–1835.

    CAS  PubMed  Google Scholar 

  35. Ingotz RA, Massague J. Transforming growth factor β stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem 1986;261:4337–4345.

    Google Scholar 

  36. Raghow R, Postlethwait AE, Keski OJ, et al. Transforming growth factor β increases steady-state levels of type I procollagen and fibronectin mRNAs posttranscriptionally in cultured human dermal fibroblasts. J Clin Invest 1987;19:1285–1288.

    Google Scholar 

  37. Gress T, Pillasch FM, Elasser HP, et al. Enhancement of transforming growth factor β1 expression in the rat pancreas during regeneration from cerulein-induced pancreatitis. Eur J Clin Invest 1994;24:679–685.

    CAS  PubMed  Google Scholar 

  38. Stein HD, Keiser HR. Proline hydroxylase activity human blood. Lancet 1970;1:106–109.

    CAS  PubMed  Google Scholar 

  39. Kuuti ER, Tuderman L, Kivirikko KI. Human prolyl hydroxylase. Eur J Biochem 1975;57:181–188.

    Google Scholar 

  40. Fine A, Goldstein RH. The effect of transforming growth factor-β on cell proliferation and collagen formation by lung fibroblasts. J Biol Chem 1987;261:3897–3902.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kato, Y., Inoue, H., Fujiyama, Y. et al. Morphological identification of and collagen synthesis by periacinar fibroblastoid cells cultured from isolated rat pancreatic acini. J Gastroenterol 31, 565–571 (1996). https://doi.org/10.1007/BF02355058

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02355058

Key words

Navigation