Scleroderma-like properties of skin from caveolin-1-deficient mice
| العنوان: | Scleroderma-like properties of skin from caveolin-1-deficient mice |
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| المؤلفون: | George Purkins, Alex Molchansky, Remedios Castello-Cros, Diana Whitaker-Menezes, Louis J. Soslowsky, David P. Beason, Renato V. Iozzo, Federica Sotgia, Michael P. Lisanti |
| المصدر: | Cell Cycle. 10:2140-2150 |
| بيانات النشر: | Informa UK Limited, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Stromal cell, Caveolin 1, Biology, Mice, Scleroderma, Localized, Dermis, Fibrosis, Report, Mitophagy, Autophagy, medicine, Animals, Humans, Myofibroblasts, Molecular Biology, Skin, Mice, Knockout, Tumor microenvironment, Scleroderma, Systemic, integumentary system, Macrophages, Cell Biology, medicine.disease, Fibronectins, Mice, Inbred C57BL, Disease Models, Animal, Mononuclear cell infiltration, medicine.anatomical_structure, Tumor progression, Immunology, cardiovascular system, Cancer research, Female, Collagen, Stromal Cells, Developmental Biology |
| الوصف: | Caveolin-1 (Cav-1), the principal structural component of caveolae, participates in the pathogenesis of several fibrotic diseases, including systemic sclerosis (SSc). Interestingly, affected skin and lung samples from patients with SSc show reduced levels of Cav-1, as compared to normal skin. In addition, restoration of Cav-1 function in skin fibroblasts from SSc patients reversed their pro-fibrotic phenotype. Here, we further investigated whether Cav-1 mice are a useful preclinical model for studying the pathogenesis of SSc. For this purpose, we performed quantitative transmission electron microscopy, as well as biochemical, biomechanical, and immuno-histochemical analysis, of the skin from Cav-1-/- null mice. Using these complementary approaches, we now show that skin from Cav-1 null mice exhibits many of the same characteristics as SSc skin from patients. These changes include a decrease in collagen fiber diameter, increased maximum stress (a measure tensile strength) and modulus (a measure of stiffness), as well as mononuclear cell infiltration. Furthermore, an increase in autophagy/mitophagy was observed in the stromal cells of the dermis from Cav-1-/- mice. These findings suggest that changes in cellular energy metabolism (e.g., a shift towards aerobic glycolysis) in these stromal cells may provide a survival mechanism in this “hostile” or pro-inflammatory microenvironment. Taken together, our results demonstrate that Cav-1-/- mice are a valuable new pre-clinical model for studying scleroderma. Most importantly, our results suggest that inhibition of autophagy and/or aerobic glycolysis may represent a new promising therapeutic strategy for halting fibrosis in SSc patients. Finally, Cav-1-/- mice are also a pre-clinical model for a “lethal” tumor microenvironment, possibly explaining the link between fibrosis, tumor progression and cancer metastasis. |
| تدمد: | 1551-4005 1538-4101 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dc110fd1ba1c3f8e7ef4b04f0cb6a58cTest https://doi.org/10.4161/cc.10.13.16227Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....dc110fd1ba1c3f8e7ef4b04f0cb6a58c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15514005 15384101 |
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