Heat Shock Protein 47: A Novel Biomarker of Phenotypically Altered Collagen-Producing Cells

Taguchi, Takashi; Nazneen, Arifa; Alshihri, Abdulmonem; Turkistani, Khadijah A.; Razzaque, Mohammed S.

doi:10.1267/ahc.11001

Cited by 27 publications

(18 citation statements)

References 68 publications

(99 reference statements)

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“…S1E). Moreover, Pax7/MyoD/myogenin −ve cells exhibited an increase in the intensity of staining for the collagen-specific molecular chaperone heat shock protein 47 (HSP47) (18, 19) (Fig. 1C).…”

Section: Resultsmentioning

confidence: 99%

A Wnt-TGFβ2 axis induces a fibrogenic program in muscle stem cells from dystrophic mice

et al. 2014

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We have previously observed that Wnt signaling activates a fibrogenic program in adult muscle stem cells, called satellite cells, during aging. We genetically labeled satellite cells in a mouse model of Duchenne muscular dystrophy to follow their fate during the progression of the disease. We observed that a fraction of satellite cells had a reduced myogenic potential and showed enhanced expression of profibrotic genes compared to age-matched controls. By combining in vitro and in vivo results, we found that expression of transforming growth factor–β2 (TGFβ2) was induced in response to elevated canonical Wnt signaling in dystrophic muscles and that the resulting increase in TGFb activity affected the behavior of satellite cells in an autocrine or paracrine fashion. Indeed, pharmacological inhibition of the TGFb pathway in vivo reduced the fibrogenic characteristics of satellite cells. These studies shed new light on the cellular and molecular mechanisms responsible for stem cell dysfunction in dystrophic muscle and may contribute to the development of more effective and specific therapeutic approaches for the prevention of muscle fibrosis.

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Section: Resultsmentioning

confidence: 99%

A Wnt-TGFβ2 axis induces a fibrogenic program in muscle stem cells from dystrophic mice

et al. 2014

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“…The pathway of the posttranslational modification of collagen is described elsewhere [29,30]. In short, after having been catalyzed by intracellular enzymes, that is, prolyl 4-hydroxylase (P4h), procollagen lysyl hydroxylase (Plod), and heat shock protein 47, procollagen produced by fibroblasts and myofibroblasts is catalyzed by a procollagen proteinase (Adamts 2) and lysyl oxidase (Lox) or members of the Lox-like (Loxl) family, after which collagen fibrils are formed.…”

Section: Resultsmentioning

confidence: 99%

Direct isolation of myofibroblasts and fibroblasts from bleomycin-injured lungs reveals their functional similarities and differences

Akamatsu

Arai

Kosugi

et al. 2013

Fibrogenesis Tissue Repair

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BackgroundMyofibroblasts play a crucial role in tissue repair. The functional similarities and differences between myofibroblasts and fibroblasts are not fully understood because they have not been separately isolated from a living body. The purpose of this study was to establish a method for the direct isolation of myofibroblasts and fibroblasts from injured lungs by using fluorescence-activated cell sorting and to compare their functions.ResultsWe demonstrated that lineage-specific cell surface markers (lin), such as CD31, CD45, CD146, EpCAM (CD326), TER119, and Lyve-1 were not expressed in myofibroblasts or fibroblasts. Fibroblasts of bleomycin-injured lungs and saline-treated lungs were shown to be enriched in linneg Sca-1high, and myofibroblasts of bleomycin-injured lungs were shown to be enriched in linneg Sca-1low CD49ehigh. Results from in-vitro proliferation assays indicated in-vitro proliferation of fibroblasts but not myofibroblasts of bleomycin-injured lungs and of fibroblasts of saline-treated lungs. However, fibroblasts and myofibroblasts might have a low proliferative capacity in vivo. Analysis of genes for collagen and collagen synthesis enzymes by qRT-PCR showed that the expression levels of about half of the genes were significantly higher in fibroblasts and myofibroblasts of bleomycin-injured lungs than in fibroblasts of saline-treated lungs. By contrast, the expression levels of 8 of 11 chemokine genes of myofibroblasts were significantly lower than those of fibroblasts.ConclusionsThis is the first study showing a direct isolation method of myofibroblasts and fibroblasts from injured lungs. We demonstrated functional similarities and differences between myofibroblasts and fibroblasts in terms of both their proliferative capacity and the expression levels of genes for collagen, collagen synthesis enzymes, and chemokines. Thus, this direct isolation method has great potential for obtaining useful information from myofibroblasts and fibroblasts.

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“…Another example is the increased minichromosome maintenance 2 and 5 expression in the epithelium of hereditary gingival fibromatosis associated with dental abnormalities compared with non-syndromic forms of HGF (21). Studies have addressed the use of Hsp47 as a biomarker in cancer (22) and fibrotic diseases (23,24), given the intimate relationship of this protein with the excessive accumulation of collagen, a feature that is present in HGF.…”

Section: Discussionmentioning

confidence: 99%

Immunoexpression of α2-integrin and Hsp47 in hereditary gingival fibromatosis and gingival fibromatosis-associated dental abnormalities

Vieira-Júnior¹,

Oliveira-Santos²,

Della-Coletta³

et al. 2013

Med Oral

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Objective: The purpose of the present study was to investigate the expression of the α2-integrin subunit and heat shock protein 47 (Hsp47) in two families with isolated gingival fibromatosis (GF) form and one family with GF associated with dental abnormalities and normal gingiva (NG). Study Design: Immunohistochemistry was performed with antibodies against α2-integrin and Hsp47 in specimens from two unrelated families with hereditary gingival fibromatosis (Families 1 and 2) and from one family with a gingival fibromatosis-associated dental abnormality (Family 3); NG samples were used for comparison. The results were analysed statistically. Results: Immunoreactivity for α2-integrin and Hsp47 was observed in the nucleus of epithelial cells of both the basal and suprabasal layer and a more discreet signal was noted in connective tissue in all study samples. Hsp47 showed higher immunoreactivity in Family 2 compared with the other families (p≤0.05). Despite the markup α2-integrin was higher in Family 3 there was no statistically significant difference between the families studied (p≥0.05). Conclusions: Our results confirmed the heterogeneity of GF, such that similar patterns of expression of the condition may show differences in the expression of proteins such as Hsp47. Although no difference in α2-integrin expression was observed between GF and NG groups, future studies are necessary to determine the exact role of this protein in the various forms of GF and whether it contributes to GF pathogenesis. Key words:Gingival fibromatosis, integrin alpha2, heat shock protein Hsp47.

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Heat Shock Protein 47: A Novel Biomarker of Phenotypically Altered Collagen-Producing Cells

Cited by 27 publications

References 68 publications

A Wnt-TGFβ2 axis induces a fibrogenic program in muscle stem cells from dystrophic mice

A Wnt-TGFβ2 axis induces a fibrogenic program in muscle stem cells from dystrophic mice

Direct isolation of myofibroblasts and fibroblasts from bleomycin-injured lungs reveals their functional similarities and differences

Immunoexpression of α2-integrin and Hsp47 in hereditary gingival fibromatosis and gingival fibromatosis-associated dental abnormalities

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