Role of bone marrow cells in the development of pancreatic fibrosis in a rat model of pancreatitis induced by a choline-deficient/ethionine-supplemented diet

Akita, Satoshi; Koyama, Koji; Kobayashi, Adam; Misawa, Ryosuke; Shimizu, Akira; Nakata, Takashi; Yokoyama, Tetsuji; Takahashi, Masafumi; Miyagawa, Shinichi

doi:10.1016/j.bbrc.2012.03.060

Cited by 19 publications

(10 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the chimeric mice were only analyzed under physiologic conditions, and no profibrotic stimulus was tested in this model (Yokota et al, 2006). In contrast, in another study, bone marrow from GFP transgenic mice were transplanted into wild-type rats, and a 23% increase in the number of GFP and αSMA-expressing cells in the pancreas was observed to peak in the early stage of an experimentally-induced but clinically-relevant pancreatitis rat model (Mathai et al, 2010; Akita et al, 2012). In all, despite substantial evidence that activated myofibroblasts are derived from local stromal fibroblasts, blood borne monocytes and monocyte-derived cells appear to facilitate fibrosis via the production of ECM and paracrine signaling with resident profibrotic cells (Murray et al, 2012).…”

Section: Sources Of Fibroblastsmentioning

confidence: 96%

Fibroblasts in fibrosis: novel roles and mediators

2014

View full text Add to dashboard Cite

Fibroblasts are the most common cell type of the connective tissues found throughout the body and the principal source of the extensive extracellular matrix (ECM) characteristic of these tissues. They are also the central mediators of the pathological fibrotic accumulation of ECM and the cellular proliferation and differentiation that occurs in response to prolonged tissue injury and chronic inflammation. The transformation of the fibroblast cell lineage involves classical developmental signaling programs and includes a surprisingly diverse range of precursor cell types—most notably, myofibroblasts that are the apex of the fibrotic phenotype. Myofibroblasts display exaggerated ECM production; constitutively secrete and are hypersensitive to chemical signals such as cytokines, chemokines, and growth factors; and are endowed with a contractile apparatus allowing them to manipulate the ECM fibers physically to close open wounds. In addition to ECM production, fibroblasts have multiple concomitant biological roles, such as in wound healing, inflammation, and angiogenesis, which are each interwoven with the process of fibrosis. We now recognize many common fibroblast-related features across various physiological and pathological protracted processes. Indeed, a new appreciation has emerged for the role of non-cancerous fibroblast interactions with tumors in cancer progression. Although the predominant current clinical treatments of fibrosis involve non-specific immunosuppressive and anti-proliferative drugs, a variety of potential therapies under investigation specifically target fibroblast biology.

show abstract

Section: Sources Of Fibroblastsmentioning

confidence: 96%

Fibroblasts in fibrosis: novel roles and mediators

2014

View full text Add to dashboard Cite

show abstract

“…One study [19] suggests that bone marrow-derived cells contribute to more than 20% of the myofibroblasts in pancreatic injury. Another study [20] suggests derivation from CD14 + monocytes, although the myofibroblast phenotype is lacking in contractile function.…”

Section: Bone Marrow-derived Progenitorsmentioning

confidence: 99%

Myofibroblasts

Phan

2013

Current Opinion in Rheumatology

View full text Add to dashboard Cite

Purpose of review Interest in the myofibroblast as a key player in propagation of chronic progressive fibrosis continues to elicit many publications, with focus on its cellular origins and the mechanisms underpinning their differentiation and/or transition. The objective of the review is to highlight this recent progress. Recent findings The epithelial origin of the myofibroblast in fibrosis has been challenged by recent studies, with the pericyte suggested as a possible precursor instead. Additional signaling pathways, including Notch, Wnt, and hedgehog, are implicated in myofibroblast differentiation. The importance of NADPH oxidase 4 was highlighted recently to suggest a potential link between cellular/oxidative stress and the genesis of the myofibroblast. Recent observations on the importance of lysophosphatidic acid in fibrosis suggest that this may be due, in part, to its ability to regulate myofibroblast differentiation. Finally, there is increasing evidence for the role of epigenetic mechanisms in regulating myofibroblast differentiation, including DNA methylation and miRNA regulation of gene expression. Summary These recent discoveries open up a whole new array of potential targets for novel antifibrotic therapies. This is of special importance given the current bleak outlook for chronic progressive fibrotic diseases, such as scleroderma, due to lack of effective therapies.

show abstract

“…Type I collagen, type III collagen, and FN are all integral components of the ECM in the pancreatic tissue (Akita et al, 2012;Yan et al, 2012). Reduction of these 3 factors can prevent deposition of the ECM in the pancreatic tissue and mitigate pancreatic fibrosis.…”

Section: Mensenchymal Stell Cells In Chronic Pancreatitismentioning

confidence: 99%

Effect of the IkBα mutant gene delivery to mesenchymal stem cells on rat chronic pancreatitis

et al. 2014

View full text Add to dashboard Cite

ABSTRACT. This study aimed to investigate the effect of inhibitors of the NF-kΒ alpha mutant gene (IkBaM) delivery to mensenchymal stem cells (MSCs) on rat chronic pancreatitis (CP). A total of 120 SpragueDawley rats were randomly divided into 6 groups of 20: Group A was injected with sterile saline solution, Group B was injected with allogenic MSCs, Group C1 was injected with allogenic IkBαM-MSCs cultured in vitro 4 h before CP modeling, Group C2 was injected with allogenic IkBαM-MSCs cultured in vitro during CP modeling, Group C3 was cultured with allogenic IkBαM-MSCs cultured in vitro 4 h after CP modeling, and Group D was injected with rAAV2-MSCs. Cytokine levels of ICAM-1, CTGF, IL-1, IL-6, IL-8, TNF-α, TIMP-1, TIMP-2, IL-10, FN, MMP-1, MMP-2, MMP-3, and MMP-9 were examined. The results indicated that allogenic IκBαM-MSCs could reduce pro- inflammatory cytokine levels and increase anti-inflammatory cytokine levels in CP. The allogenic IkBαM-MSCs reduced the activation and promoted the apoptosis of pancreatic stellate cells in the rat model of CP. IkBαM-MSCs influenced the proliferation and apoptosis of pancreatic stellate cells by regulating the activation of the PPAR, MAPK, mTOR, TGF-β, NOD-like receptor, Notch, WNT, TGF-β1-SMAD-2/3, and P53 signal transduction pathways.

show abstract

Role of bone marrow cells in the development of pancreatic fibrosis in a rat model of pancreatitis induced by a choline-deficient/ethionine-supplemented diet

Cited by 19 publications

References 37 publications

Fibroblasts in fibrosis: novel roles and mediators

Fibroblasts in fibrosis: novel roles and mediators

Myofibroblasts

Effect of the IkBα mutant gene delivery to mesenchymal stem cells on rat chronic pancreatitis

Contact Info

Product

Resources

About