An ex vivo model for functional studies of myofibroblasts

Kilarski, Witold W.; Jura, Natalia; Gerwins, Pär

doi:10.1038/labinvest.3700255

Cited by 24 publications

(17 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, alpha-SMC actin-positive cells were only evident in the lumen of 2-week-old occlusions. These cells also were desmin negative, which led us to identify the cell type as a myofibroblast (16). At all later time points, the lumen cells were alpha-SMC actinnegative, except in the media of luminal microvessels.…”

Section: Methodsmentioning

confidence: 96%

Natural History of Experimental Arterial Chronic Total Occlusions

Jaffe

Leung

Munce

et al. 2009

Journal of the American College of Cardiology

View full text Add to dashboard Cite

show abstract

Section: Methodsmentioning

confidence: 96%

Natural History of Experimental Arterial Chronic Total Occlusions

Jaffe

Leung

Munce

et al. 2009

Journal of the American College of Cardiology

View full text Add to dashboard Cite

show abstract

“…Furthermore, TGF-b1-induced proliferation of fibroblasts is mediated through the release of extracellular FGF-2 since FGF-2-blocking antibodies inhibited the proliferation of fibroblasts [19,61]. Finally, it has been shown that both PDGF and FGF-2 are important factors in the migration of myofibroblasts [64], suggesting that blockade of both pathways might be required to interfere with myofibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of PDGF, VEGF and FGF signalling attenuates fibrosis

Chaudhary¹,

Roth²,

Hilberg³

et al. 2007

European Respiratory Journal

334

259

View full text Add to dashboard Cite

BIBF 1000 is a small molecule inhibitor targeting the receptor kinases of plateletderived growth factor (PDGF), basic fibroblast growth factor and vascular endothelial growth factor, which have known roles in the pathogenesis of pulmonary fibrosis.The anti-fibrotic potential of BIBF 1000 was determined in a rat model of bleomycin-induced lung fibrosis and in an ex vivo fibroblast differentiation assay. Rats exposed to a single intratracheal injection of bleomycin were treated with BIBF 1000 starting 10 days after bleomycin administration. To gauge for anti-fibrotic activity, collagen deposition and pro-fibrotic growth factor gene expression was analysed in isolated lungs. Furthermore, the activity of BIBF 1000 was compared with imatinib mesylate (combined PDGF receptor, c-kit and c-abl kinase inhibitor) and SB-431542 (transforming growth factor (TGF)-b receptor I kinase inhibitor) in an ex vivo TGF-bdriven fibroblast to myofibroblast differentiation assay, performed in primary human bronchial fibroblasts.Treatment of rats with BIBF 1000 resulted in the attenuation of fibrosis as assessed by the reduction of collagen deposition and the inhibition of pro-fibrotic gene expression. In the cellular assay both SB-431542 and BIBF 1000 showed dose-dependent inhibition of TGF-b-induced differentiation, whereas imatinib mesylate was inactive.BIBF 1000, or related small molecules with a similar kinase inhibition profile, may represent a novel therapeutic approach for the treatment of idiopathic pulmonary fibrosis.

show abstract

“…It has been reported that ER-b controls platelet-derived growth factor (PDGF), 28 a cytokine regulating the growth and the differentiation of fibroblasts into myofibroblasts. 29 Interestingly, PDGF is commonly expressed together with its receptors in the stroma of phyllodes tumor and rarely in fibroadenoma. 30 An ER-b-PDGF pathway could therefore be involved in the smooth muscle differentiation in these lesions.…”

Section: Er-b In Breast Fibroepithelial Lesionsmentioning

confidence: 99%

Estrogen receptor-β is expressed in stromal cells of fibroadenoma and phyllodes tumors of the breast

et al. 2006

View full text Add to dashboard Cite

An estrogen dependency has been suggested for the growth of fibroadenomas: however, thus far, none of the steroid hormone receptors acting on breast tissues has been demonstrated in the stroma of breast fibroepithelial lesions. In this study, the expression of estrogen receptor (ER)-a and -b was investigated by immunohistochemistry in 33 fibroadenomas and in 30 benign, three borderline and seven malignant phyllodes tumors, all with spindle cell growth and in one distant metastasis. In addition, the presence of ER-b mRNA and its variants was evaluated by RT-PCR in microdissected stroma. The possible correlation between hormone receptor expression and differentiation processes of stromal cells was investigated by smooth muscle actin and calponin immunostaining. ER-b was the only hormone receptor expressed by stroma of fibroadenomas and phyllodes tumors, both at protein and mRNA level. The highest percentage of ER-b was observed in fibroadenomas with cellular stroma and in phyllodes tumors. In both lesions, ER-b-positive stromal cells showed expression of smooth muscle actin and/or calponin, as demonstrated by double immunostaining. In addition, the mean age at diagnosis was significantly lower in patients with ER-b-positive vs ER-b-negative fibroadenomas. In contrast, in phyllodes tumors, ER-b expression was higher in older patients. In conclusion, (i) only ER-b is detected in the stroma of fibroadenomas and phyllodes tumors; (ii) its expression correlates with the expression of smooth muscle markers and suggests a role of ER-b in myofibroblastic differentiation of stromal cells. These two results, together with the young age of patients carrying fibroadenomas with highly ER-b-positive stroma cells, may further indicate a hormone-receptor mechanism involved in regulating the growth of fibroadenomas. Conversely, the older age of patients with ER-b-rich phyllodes tumors suggests that mechanisms, probably independent from estrogen stimulation, act on the growth of these tumors.

show abstract

An ex vivo model for functional studies of myofibroblasts

Cited by 24 publications

References 29 publications

Natural History of Experimental Arterial Chronic Total Occlusions

Natural History of Experimental Arterial Chronic Total Occlusions

Inhibition of PDGF, VEGF and FGF signalling attenuates fibrosis

Estrogen receptor-β is expressed in stromal cells of fibroadenoma and phyllodes tumors of the breast

Contact Info

Product

Resources

About