Activated Hepatic Stellate Cells Are Dependent on Self-collagen, Cleaved by Membrane Type 1 Matrix Metalloproteinase for Their Growth

Birukawa, Naoko; Murase, Kazuyuki; Sato, Yasushi; Kosaka, Akemi; Yoneda, Akihiro; Nishita, Hiroki; Fujita, Ryosuke; Nishimura, Miyuki; Ninomiya, Takafumi; Kajiwara, Keiko; Miyazaki, Miyono; Nakashima, Yasuhiko; Ota, Sigenori; Murakami, Yuya; Tanaka, Yasunobu; Minomi, Kenjiro; Tamura, Yasuaki; Niitsu, Yoshiro

doi:10.1074/jbc.m113.544494

Cited by 32 publications

(30 citation statements)

References 29 publications

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“…In this regard, it may be an interesting challenge to explore the possibility in the future that MT1-MMP cleaved collagen from aPSCs stimulates replication of PACs in a paracrine manner, since our previous observation clearly demonstrated that collagen secreted from activated hepatic stellate cells (aHSCs) sustains their own survival in an autocrine manner after it is cleaved by membrane type1 metalloproteinase (MT1-MMP) [25]. …”

Section: Discussionmentioning

confidence: 99%

“…The PSCs were transfected with siRNA HSP47 with the same the method as applied for hepatic stellate cells [24,25]. …”

Section: Methodsmentioning

confidence: 99%

“…We further revealed that those stellate cells treated with the siRNA-HSP47 underwent apoptosis, because they were dependent on self-collagen cleaved by membrane type1 matrix metalloproteinase (MT1-MMP) for their growth [25]. …”

Section: Introductionmentioning

confidence: 99%

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Involvement of Pancreatic Stellate Cells in Regeneration of Remnant Pancreas after Partial Pancreatectomy

et al. 2016

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Background and objectivesMechanism of regeneration of remnant pancreas after partial pancreatectomy (PX) is still unknown. In this study, effect of siRNA against the collagen specific chaperone, HSP47, which inhibits collagen secretion from activated pancreas stellate cells (aPSCs), and induces their apoptosis, on regeneration of remnant pancreas was determined.MethodsPancreatectomy was performed according to established methods. Proliferation of cells was assessed by BrdU incorporation. Immunostaining of HSP47 was employed to identify PSCs. Progenitor cells were identified by SOX9 staining. Acinar cells were immunostained for amylase. Co-culture of acinar cells with aPSCs were carried out in a double chamber with a cell culture insert. siRNA HSP47 encapsulated in vitamin A-coupled liposome (VA-lip siRNA HSP47) was delivered to aPSCs by iv injection.ResultsIn remnant pancreas of 90% PX rat, new areas of foci were located separately from duodenal areas with normal pancreatic features. After PX, BrdU uptake of acinar cells and islet cells significantly increased, but was suppressed by treatment with VA-lip siRNA HSP47. BrdU uptake by acinar cells was augmented by co-culturing with aPSCs and the augmentation was nullified by siRNA HSP47. BrdU uptake by progenitor cells in foci area was slightly enhanced by the same treatment. New area which exhibited intermediate features between those of duodenal and area of foci, emerged after the treatment.ConclusionaPSCs play a crucial role in regeneration of remnant pancreas, proliferation of acinar and islet cells after PX through the activity of secreted collagen. Characterization of new area emerged by siRNA HSP47 treatment as to its origin is a future task.

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Section: Discussionmentioning

confidence: 99%

“…The PSCs were transfected with siRNA HSP47 with the same the method as applied for hepatic stellate cells [24,25]. …”

Section: Methodsmentioning

confidence: 99%

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Involvement of Pancreatic Stellate Cells in Regeneration of Remnant Pancreas after Partial Pancreatectomy

et al. 2016

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“…65 Also, MT1-MMP participates in the regulation of fibrosis progression as it cleaves intramolecular RGD motifs of collagen produced by activated HSCs and thus controls aVβ1 activation, providing a survival signal via PI3K/AKT/IκB. 69 During the entire progress of liver fibrosis, the expression of main inhibitor of MMPs, TIMP-1, is increased to regulate the elevated MMP activity. TIMP-1 has distinct functions in establishment and resolution of fibrosis.…”

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confidence: 99%

Metalloproteinases in liver fibrosis: current insights

Zbodakova¹,

Chalupský²,

Turečková³

et al. 2017

MNM

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Liver fibrosis is defined by excessive deposition of extracellular matrix. The fibrotic conditions result from the imbalance between synthesis and deposition of fibrous tissues and decomposition of these matrix proteins. This process can be reversed as a regular part of the healing process after hepatic damage or can become chronic. When the protein matrix synthesis predominates and the decomposition is suppressed, fibrosis will progress into irreversible cirrhosis or steatosis. Among the molecular players involved in fibrotic liver diseases, metalloproteinases of matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase (ADAM) families are critical in the development of liver fibrosis and its resolution. Previously, MMPs were recognized as extracellular matrix degrading enzymes. Currently, they are also known as mediators in a variety of processes related to immunity and tissue repair. In this article, we have reviewed the models of liver fibrosis and findings on MMPs and ADAMs in hepatic fibrosis conditions.

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“…The most basic biological functionality in using two-dimensional (2D) cultures in combination with ECM is achieved by addition of the commonly used Arg-Gly-Asp (RGD) peptide as cell-adhesive ligands. Until today, the RGD peptide is a known adhesive domain of several ECM components, such as that involved in the binding of fibronectin [48], an important assembler of the collagen matrix, to the α5β1 integrin receptor [49] with the presence of the intra-molecular RGD motifs in collagen [50].…”

Section: Single Cell Culture and 2d: Importance Of Adhesion Arg-gly-mentioning

confidence: 99%

Hepatic Stellate Cell Culture Models

Rombouts

2015

Stellate Cells in Health and Disease

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Activated Hepatic Stellate Cells Are Dependent on Self-collagen, Cleaved by Membrane Type 1 Matrix Metalloproteinase for Their Growth

Cited by 32 publications

References 29 publications

Involvement of Pancreatic Stellate Cells in Regeneration of Remnant Pancreas after Partial Pancreatectomy

Involvement of Pancreatic Stellate Cells in Regeneration of Remnant Pancreas after Partial Pancreatectomy

Metalloproteinases in liver fibrosis: current insights

Hepatic Stellate Cell Culture Models

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