دورية أكاديمية
Stromal regulation of vessel stability by MMP14 and TGFbeta.
| العنوان: | Stromal regulation of vessel stability by MMP14 and TGFbeta. |
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| المؤلفون: | Sounni, Nor Eddine, Dehne, K., van Kempen, L., Egeblad, M., Affara, N. I., Cuevas, I., Wiessen, J., Junankar, S., Kortes, L., Lee, J., Shen, J., Morrison, C. J., Overall, C. M., Krane, S. M., Werb, Z., Boudreau, N., Coussens, L. M. |
| المصدر: | Disease Models and Mechanisms, 3, 317-332 (2010-05) |
| بيانات النشر: | The Company of Biologists Ltd |
| سنة النشر: | 2010 |
| المجموعة: | University of Liège: ORBi (Open Repository and Bibliography) |
| مصطلحات موضوعية: | vascular leakage, TGFbeta, MMP14/MT1-MMP, extracellular matrix, type I collagen, Life sciences, Biotechnology, Sciences du vivant, Biotechnologie |
| الوصف: | peer reviewed ; Innate regulatory networks within organs maintain tissue homeostasis and facilitate rapid responses to damage. We identified a novel pathway regulating vessel stability in tissues involving matrix metalloproteinase 14 (MMP14) and transforming growth factor beta (TGFbeta)1. Whereas plasma proteins rapidly extravasate out of vasculature in wildtype mice following acute damage, short-term treatment of mice in vivo with a broad-spectrum metalloproteinase inhibitor, neutralizing antibodies to TGFbeta1 or an ALK5 inhibitor significantly enhanced vessel leakage. In contrast, in a mouse model of age-related dermal fibrosis where MMP14 activity and TGFbeta bioavailability are chronically elevated, or in mice that ectopically express TGFbeta in epidermis, cutaneous vessels are resistant to acute leakage. Characteristic responses to tissue damage are reinstated if fibrotic mice are pre-treated with metalloproteinase inhibitors or TGFbeta signaling antagonists. Neoplastic tissues on the other hand are in a constant state of tissue damage and exhibit altered hemodynamics due to hyperleaky angiogenic vasculature. In two distinct transgenic mouse tumor models, inhibition of ALK5 further enhanced vascular leakage into interstitium and facilitated increased delivery of high molecular weight compounds into premalignant tissue and tumors. Taken together, these data define a central pathway involving MMP14 and TGFbeta that mediate vessel stability and vascular response to tissue injury. Antagonists of this pathway could be therapeutically exploited to improve delivery of therapeutics or molecular contrast agents into tissues where chronic damage or neoplastic disease limits their efficient delivery. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1754-8411 1754-8403 |
| العلاقة: | urn:issn:1754-8411; urn:issn:1754-8403; https://orbi.uliege.be/handle/2268/63418Test; info:hdl:2268/63418; https://orbi.uliege.be/bitstream/2268/63418/1/Sounni%20DMM2010%20.pdfTest; scopus-id:2-s2.0-77952212733; info:pmid:20223936 |
| DOI: | 10.1242/dmm.003863 |
| الإتاحة: | https://doi.org/10.1242/dmm.003863Test https://orbi.uliege.be/handle/2268/63418Test https://orbi.uliege.be/bitstream/2268/63418/1/Sounni%20DMM2010%20.pdfTest |
| حقوق: | open access ; http://purl.org/coar/access_right/c_abf2Test ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.562C417 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 17548411 17548403 |
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| DOI: | 10.1242/dmm.003863 |