Ligands of Peroxisome Proliferator-activated Receptor-γ Block Activation of Pancreatic Stellate Cells

Regulation of myofibroblast transdifferentiation by DNA methylation and MeCP2: implications for wound healing and fibrogenesis

“…2,4,9 The myofibroblast generated from these distinct cellular sources is very similar in terms of their key stimulatory growth factors (TGFb and PDGF), expression of contractile proteins (a-SMA), secretion of fibrogenic factors (types I and III collagen and TIMP-1) and their expression/activity of transcriptional regulators PPARg, NF-kB and AP-1. [19][20][21][22] It is therefore not unreasonable to speculate that the transdifferentiation process responsible for generating these shared phenotypic characteristics is underpinned by a common epigenetic blueprint. Finally, there are obvious implications of our findings for the clinic, especially as we have identified MeCP2 expression in human liver disease.…”

“…[2][3][4] In support of this concept there are many reports describing alterations in expression and/or activity of key transcription factors such as PPARs, NF-kB and AP-1 common to MTD of distinct organ-specific myofibroblast-precursor cells. [19][20][21][22] However, no single transcription factor or combinations of transcription factors are so far described as responsible for exerting global control of MTD.…”

Alcohol, Signaling, and ECM Turnover

“…During alcoholic pancreatic injury, PSCs are activated in a paracrine fashion, by growth factors, proinflammatory cytokines, and oxidant stress (Apte et al, 2005a) and are the major source of collagen deposition in fibrotic pancreas . The likely activating factors include proliferative and pro-fibrogenic growth factors such as platelet derived growth factor (PDGF) and TGF-b, as well as oxidant stress generated within the tissues by oxidative metabolism of alcohol to acetaldehyde and subsequently to acetate Masamune et al, 2002). Notably, PSCs can also synthesize endogenous cytokines resulting in an autocrine loop of cell activation (Shek et al, 2002;Sparmann et al, 2005).…”

Establishment and characterization of a rat pancreatic stellate cell line by spontaneous immortalization

“…SIPS cells also expressed extracellular matrix proteins type I collagen ( Figure 1E) and fibronectin ( Figure 1F). SIPS cells expressed prolyl hydroxylases (α, β) ( Figure 1G, H), that are key enzymes in the hydroxylation of the proline residues in procollagen and are useful markers of collagen synthesis [7] . These results suggest that SIPS cells shared many phenotypical and functional characteristics with primary, culture-activated PSCs.…”

“…There is accumulating evidence that PSCs, like hepatic stellate cells, are responsible for the development of pancreatic fibrosis [3,4,6] . Furthermore, PSCs might participate in the pathogenesis of acute pancreatitis through the expression of monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 [7,8] . The activation of signaling pathways such as p38 mitogen-activated protein (MAP) kinase [9] is likely to play a key role in PSC activation.…”