[3] Synthesis, deposition, maturation and remodelling of the fibrous connective tissue can be protective, however when persistent it impedes regular pancreatic function.
[2] Following inflammation or injury to the pancreas, quiescent PaSCs are activated to myofibroblast like cells, which expresses α- smooth muscle actin.
[2] The activated PaSCs then grow in number, migrate and secrete extracellular matrix components such as type I collagen, chemokines and cytokines.
[6] The production of these factors indicates the presence of autocrine loops that perpetuate PaSC activation, promoting the development of fibrosis.
[6] Protein kinases such as MAPKs are primary mediators of activating signals initiated by the growth factors, angiotensin II and ethanol.
[2] Following activation, PaSCs migrate to areas of tissue damage and contract, phagocytose, and induce products that regulate the ECM through facilitating repair or by promoting fibrosis.
[2] The migration of PaSCs is modulated by Indian hedgehog (IHH), a peptide that is involved in pancreatic development, patterning and differentiation.
[8] Ethanol at clinically relevant concentrations causes α-SMA expression and collagen production in PaSCs but produce a minimal effect on cell proliferation.
[12] After pancreatic damage occurs, pathologic events such as interstitial oedema, necrosis of parenchymal cells, activation and proliferation of PaSCs take place.
[2] Activated PaSCs are located in areas of major necrosis and inflammation that harbour cytokines, growth factors and reactive oxygen species.
[2] α-SMA-expressing cells in fibrotic areas yield MRNA encoding pro-collagen α1I, indicating that activated PaSCs are the predominant source of collagen in pancreatic fibrosis.
[2] Activated PaSCs in the tumour desmoplasia of human pancreatic cancers express α-SMA and co-localise with MRNA encoding pro-collagen α1I.
[2] A symbiotic relationship exists between pancreatic adenocarcinoma cells and PaSCs, which leads to an overall increase in the rate of growth of the tumour.
[2] For example, culture supernatants from human pancreatic tumour cell lines induce PaSC proliferation and the production of ECM proteins.
[2] Connective tissue growth factor is involved in the pathogenesis of fibrotic diseases and is predominantly found in PaSCs through regulation by TGF-β.
[13] The cellular response to hypoxia is mediated by the transcription factor HIF-1, which is a heterodimer protein composed of α and β subunits.
[13] Overall, PSCs are linked to ECM production and remodeling, intra-tumoral hypoxia, resistance/barrier to chemotherapy, proliferation, invasion, migration, reduced apoptosis, angiogenesis, immune suppression, and pain factors.
[6] Agents such as angiotensin receptor blockers, serine protease inhibitors and adenine dinucleotide phosphate oxidase inhibit the activation and function of PaSCs.
[6] Camostat mesilate, an oral protease inhibitor, that is used to treat patients with chronic pancreatitis inhibited the proliferation and MCP-1 production in PaSCs in vitro.