Effect of mast cell–derived mediators and mast cell–related neutral proteases on human dermal fibroblast proliferation and type I collagen production

Abe, Masatoshi; Kurosawa, Motohiro; Ishikawa, Osamu; Miyachi, Yoshiki

doi:10.1067/mai.2000.106058

Cited by 70 publications

(52 citation statements)

References 34 publications

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“…The notion that PGs and their receptors regulate proliferation and type I collagen synthesis in fibroblasts was suggested by earlier studies (15,16,35). When we tested different PGs known to interact with different prostanoid receptors, we observed that only PGJ 2 and its metabolite, 15d-PGJ 2 , acting via the nuclear receptor PPAR␥, but not other members of the PG family increase HFFF2 proliferation.…”

Section: Discussionsupporting

confidence: 56%

“…Effects of tryptase on fibroblast proliferation, chemotaxis, and collagen production were observed by other authors (1,11,15), identifying tryptase as a fibroblast growth factor. Unexpectedly, we now find that tryptase and the PAR2 agonist peptide SLIGKV induce the PG-synthesizing enzyme, COX2.…”

Section: Discussionmentioning

confidence: 58%

“…Other reports indicated that IL-1␤ (13) or secretory phospholipase A (14) are involved in COX2 induction and PG synthesis. Importantly, it seems that PGs, including PGD 2 , can regulate fibroblast proliferation and type I collagen production (15,16). Although details of this action are not well known, this result may imply a direct role for PGs in fibrosis.…”

mentioning

confidence: 99%

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Proliferative action of mast-cell tryptase is mediated by PAR2, COX2, prostaglandins, and PPARγ: Possible relevance to human fibrotic disorders

Frungieri

Weidinger

Meineke

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

235

229

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Mast-cell products can stimulate fibroblast proliferation, implying that these cells are key players in fibrosis. One mast-cell product, the serine protease tryptase, is known to activate protease-activated receptor 2 (PAR2) and cause proliferation of fibroblasts. We found that recombinant tryptase, human mastcell (HMC-1) supernatant, which contains tryptase, and the PAR2-activating peptide SLIGKV exert fibroproliferative actions in human fibroblasts. Here we report insights into this action, which after activation of PAR2 leads to increased expression of cyclooxygenase 2 (COX2), a key enzyme in the biosynthesis of prostaglandins, and consequently to enhanced prostaglandin synthesis. Subsequent cell proliferation is mediated by the prostaglandin 15-deoxy-⌬ 12,14 -prostaglandin J2, which acts via the nuclear peroxisome proliferator-activated receptor ␥ (PPAR␥). Fibroblast proliferation induced by tryptase and PAR2 agonist peptide can be blocked by antagonists of COX2 and PPAR␥, implying that the proliferative effect of tryptase is PAR2-initiated but depends on COX2, 15-deoxy-⌬ 12,14 -prostaglandin J2, and PPAR␥. This previously uncharacterized pathway could be of relevance for human fibrotic diseases. For instance, increased numbers of activated mast cells are correlated with fibrosis in testes of infertile men. In these cases all components of the signaling pathway of tryptase were detected as well as expression of COX2. Therefore, our study describes as-yet-unknown interactions between mast cells and fibroblasts, which could be relevant for human fibrotic diseases.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 58%

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Proliferative action of mast-cell tryptase is mediated by PAR2, COX2, prostaglandins, and PPARγ: Possible relevance to human fibrotic disorders

Frungieri

Weidinger

Meineke

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

235

229

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“…23,24 Mast cells also release CPA3 and mast cell tryptase, both of which have known proliferative effects on fibroblasts. 25 Despite these potential physiological influences on tendon repair, the current study suggests that mast cells are not an absolute requirement for tendon repair to occur. This finding is consistent with wound healing studies in mast cell-deficient (W/Wv) mice in which mast cells were not essential for healing, but did influence the quality of repair.…”

Section: Mast Cells In Patellar Tendon Injurymentioning

confidence: 65%

Sodium cromolyn reduces expression of CTGF, ADAMTS1, and TIMP3 and modulates post‐injury patellar tendon morphology

Sharma

Abraham

Sampaio

et al. 2010

Journal Orthopaedic Research

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The purpose of this study was to determine whether administration of a mast cell inhibitor (sodium cromolyn, SC) would influence tendon repair and extracellular matrix gene expression following acute injury. CD1 mouse patellar tendons were unilaterally injured and mast cell prevalence was determined. The effect of SC injection on tendon hypercellularity, cross-sectional area, collagen organization, and expression of extracellular matrix-related genes was examined. Mast cell prevalence was markedly increased in injured patellar tendons ( p ¼ 0.009), especially at 8 weeks post-injury ( p ¼ 0.025). SC injection increased collagen organization compared to uninjected animals at 4 weeks and attenuated the development of tendon hypercellularity and tendon thickening post-injury. Expression of CTGF, ADAMTS1, and TIMP3 in injured tendon was reduced in the SC group. SC injections moderated the structural alterations of healing tendon in association with downregulation of several genes associated with tendon fibrosis. This work corroborates previous findings pointing to a role of mast cells in tendon repair. ß

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“…Only recently have studies been carried out to address the effects of mast cells secretory products on ®broblasts. Tryptase from mast cells has been shown to stimulate collagen expression, proliferation, and migration by ®broblasts implicating this protease as being responsible for modulation of ®broblast behavior (Gruber et al, 1997;Abe et al, 1998Abe et al, , 2000. Supporting this contention are recent data indicating that stimulation of ®broblast proliferation by mast cells is attenuated by serine protease inhibitors (Akers et al, 2000).…”

Section: Discussionmentioning

confidence: 75%

Effects of mast cells on the behavior of isolated heart fibroblasts: Modulation of collagen remodeling and gene expression

Almeida

Mustin

Forman

et al. 2002

Journal Cellular Physiology

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The extracellular matrix plays a critical role in the development and maintenance of the vertebrate heart. Changes in the accumulation, composition, or organization of the extracellular matrix are known to deleteriously affect heart function. Mast cells are thought to stimulate collagen expression and fibroblast proliferation accompanying fibrosis in some organs; however, the effects of mast cells on the heart interstitium are largely unexplored. The present studies were carried out to determine the effects of mast cells on isolated heart fibroblasts. Several in vitro assays were used including collagen gel contraction to examine the effects of mast cells on the function of isolated fibroblasts. Neonatal heart fibroblasts were cultured either with mast cells, mast cell-conditioned medium, or mast cell extracts, and their ability to contract collagen gels measured. Results from these experiments indicated that mast cells inhibit heart fibroblast migration and contraction of 3-dimensional collagen gels. Further experiments indicated that incubation of neonatal heart fibroblasts with extracts of mast cells altered the expression of collagen, matrix metalloproteases, and matrix receptors of the integrin family. These studies suggest that mast cells play an important role in the regulation of the cardiac interstitial matrix. Further studies are warranted to determine the mechanisms whereby mast cells modulate fibroblast activity.

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Effect of mast cell–derived mediators and mast cell–related neutral proteases on human dermal fibroblast proliferation and type I collagen production

Cited by 70 publications

References 34 publications

Proliferative action of mast-cell tryptase is mediated by PAR2, COX2, prostaglandins, and PPARγ: Possible relevance to human fibrotic disorders

Proliferative action of mast-cell tryptase is mediated by PAR2, COX2, prostaglandins, and PPARγ: Possible relevance to human fibrotic disorders

Sodium cromolyn reduces expression of CTGF, ADAMTS1, and TIMP3 and modulates post‐injury patellar tendon morphology

Effects of mast cells on the behavior of isolated heart fibroblasts: Modulation of collagen remodeling and gene expression

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