Mv. Apte et al., Pancreatic stellate cells are activated by proinflammatory cytokines: implications for pancreatic fibrogenesis, GUT, 44(4), 1999, pp. 534-541
Background-The pathogenesis of pancreatic fibrosis is unknown. In the liver
stellate cells play a major role in fibrogenesis by synthesising increased
amounts of collagen and other extracellular matrix (ECM) proteins when act
ivated by profibrogenic mediators such as cytokines and oxidant stress.
Aims-To determine whether cultured rat pancreatic stellate cells produce co
llagen and other ECM proteins, and exhibit signs of activation:when exposed
to the cytokines platelet derived growth factor (PDGF) or transforming gro
wth factor beta (TGF-beta).
Methods-Cultured pancreatic stellate cells were immunostained for the ECM p
roteins procollagen III, collagen I, laminin, and fibronectin using specifi
c polyclonal antibodies. For cytokine studies, triplicate wells of cells we
re incubated with increasing concentrations of PDGF or TGF-beta.
Results-Cultured pancreatic stellate cells stained strongly positive for al
l ECM proteins tested. Incubation of cells with I, 5, and 10 ng/ml PDGF led
to a significant close related increase in cell counts as well as in the i
ncorporation of H-3-thymidine into DNA, Stellate cells exposed to 0.25, 0.5
, and 1 ng/ml TGF-beta showed a dose dependent increase in alpha smooth-mus
cle actin expression and increased collagen synthesis; In addition, TGF-bet
a increased the expression of PDGF receptors on stellate cells.
Conclusions-Pancreatic stellate cells produce collagen and other extracellu
lar matrix proteins, and respond to the cytokines PDGF and TGF-beta by incr
eased proliferation and increased collagen synthesis. These results suggest
an important role for stellate cells in pancreatic fibrogenesis.