Evaluating the cutaneous involvement in scleroderma: torsional stiffness revisited

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 pre-clinical model for studying the pathogenesis of SSc. For this purpose, we performed quantitative transmission electron microscopy, as well as biochemical 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, including a decrease in collagen fiber diameter, increased tensile strength, and 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 be a survival mechanism in this "hostile" or pro-inflammatory microenvironment. Taken together, our results demonstrate that Cav-1 (-/-) null 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 (-/-) null mice are also a pre-clinical model for a "lethal" tumor micro-environment, possibly explaining the link between fibrosis, tumor progression, and cancer metastasis.

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“…Increases in skin strength and stiffness have been reported to be characteristics of fibrotic tissues, including Ssc skin. 12,43…”

Section: Resultsmentioning

confidence: 99%

Scleroderma-like properties of skin from caveolin-1-deficient mice

Castelló-Cros

Whitaker‐Menezes²,

Molchansky³

et al. 2011

Cell Cycle

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“…It is vitally important to have an experimental method, which can measure and quantify the mechanical properties of skin for different site locations and different individuals. Such data would contribute to many areas, from the tracking of skin diseases [36] to testing the efficacy of moisturisers [37]. In this study, the in vivo mechanical response of skin was measured by applying a rich set of three-dimensional deformations to different points of the arms of 20 volunteers.…”

Section: Discussionmentioning

confidence: 99%

Measurement of the force–displacement response of in vivo human skin under a rich set of deformations

Flynn

Taberner

Nielsen

2011

Medical Engineering & Physics

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“…A number of techniques have been developed for quantitative evaluation of the mechanical properties of skin. These techniques include durometer, indentation, ballistometry, twistometry, and the suction method [1,6,7]. The suction method is the measurement of skin displacement caused by a suction force.…”

Section: Introductionmentioning

confidence: 99%