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Transforming growth factor-beta (TGF-beta 1) inhibits pancreatic acinar cell growth
C D Logsdon1, L Keyes, R D Beauchamp
1Department of Physiology, University of Michigan, Ann Arbor 48109.
Abstract:
Effects of transforming growth factor (TGF)-beta 1 on mouse pancreatic acinar cell growth and rapid intracellular responses to cholecystokinin (CCK) were examined in vitro. TGF-beta 1 inhibited [3H]thymidine incorporation stimulated by either the CCK analogue caerulein, epidermal growth factor, or insulin. TGF-beta 1 inhibition of growth stimulated by a maximal dose of caerulein (1 nM) was dose dependent with one-half maximal effects occurring at approximately 5 pM and maximal inhibition seen with 30 pM. In contrast to its effects on CCK-stimulated [3H]thymidine incorporation, TGF-beta 1 had no effect on CCK-stimulated increases in amylase release or intracellular Ca2+ concentration. To determine whether TGF-beta 1 might be an autocrine growth regulator, pancreatic mRNA was probed for the presence of TGF-beta 1 transcripts. TGF-beta 1 mRNA was not detected in whole pancreas but was detectable with increasing abundance over time in primary cultures of pancreatic acinar cells. The appearance of the TGF-beta 1 mRNA corresponded to the period of rapid cellular proliferation in vitro. These results suggest that TGF-beta 1 may be an autocrine growth inhibitor in the pancreas and that the inhibitory effects of TGF-beta 1 on pancreatic acinar cell growth occur at sites distal to those involved in stimulus-secretion coupling.
Insights
Transforming growth factor-beta 1 (TGF-beta 1) inhibits mouse pancreatic acinar cell growth by reducing thymidine incorporation. This TGF-beta 1 effect on pancreatic cell growth is dose-dependent and occurs independently of CCK-stimulated secretion.
Area of Science:
- Cell Biology
- Endocrinology
- Gastroenterology
Background:
- Pancreatic acinar cells are crucial for digestion.
- Growth factors regulate pancreatic cell function.
- Autocrine signaling plays a role in tissue homeostasis.
Purpose of the Study:
- To investigate the effects of transforming growth factor-beta 1 (TGF-beta 1) on mouse pancreatic acinar cell proliferation.
- To examine the relationship between TGF-beta 1 and cholecystokinin (CCK)-mediated signaling.
- To determine if TGF-beta 1 acts as an autocrine regulator in pancreatic acinar cells.
Main Methods:
- In vitro culture of mouse pancreatic acinar cells.
- Measurement of [3H]thymidine incorporation to assess cell growth.
- Analysis of amylase release and intracellular calcium concentration.
- Detection of TGF-beta 1 mRNA using Northern blotting.
Main Results:
- TGF-beta 1 significantly inhibited [3H]thymidine incorporation stimulated by caerulein, EGF, or insulin in a dose-dependent manner.
- TGF-beta 1 did not affect CCK-stimulated amylase release or intracellular Ca2+ levels.
- TGF-beta 1 mRNA was detected in cultured pancreatic acinar cells, increasing with time and correlating with proliferation.
Conclusions:
- TGF-beta 1 acts as a potent inhibitor of pancreatic acinar cell proliferation in vitro.
- The inhibitory effects of TGF-beta 1 on cell growth are distinct from its lack of influence on CCK-mediated stimulus-secretion coupling.
- TGF-beta 1 may function as an autocrine growth inhibitor in the pancreas, with its effects occurring downstream of initial stimulus-response pathways.