Title

SPARC and extracellular matrix production after asbestos exposure

Presenter Information

Cicily Tatsey-Bull Calf

Presentation Type

Poster

Abstract

Exposures to asbestos fibers by inhalation cause multiple asbestos-related diseases including asbestosis, lung cancer and mesothelioma. In asbestosis, the major consequence of asbestos exposure is increased extracellular matrix (ECM) production, primarily the deposition of collagen in the lungs. Previously our lab has shown that RNA expression of secreted protein acidic and rich in cysteine (SPARC) was increased in mouse lungs exposed to several types of asbestos fibers. SPARC is a matricellular protein involved in the regulation of ECM-cell interactions through modulation of growth factor activity. The central hypothesis to be tested in our studies is that the expression of SPARC is a significant step in the development of lung fibrosis through the modulation of ECM production. To test our hypothesis, we used expression of small interfering RNA (siRNA) to decrease SPARC production by facilitating the degradation of Sparc RNA. This was tested both in vitro with primary lung fibroblast cultures, as well as in vivo in a mouse model. Primary lung fibroblast cultures were established from C57Bl/6 mice and exposed to crocidolite asbestos to induce increased ECM production. Subsequently, the cultures were exposed to lentivirus containing siRNA sequences specifically designed to inhibit SPARC. Western blots will be performed to analyze SPARC and collagen production. Experiments are ongoing and current results will be presented. The ultimate goal of this project is to determine if control of SPARC expression has potential as a treatment for the fibrosis caused by asbestos exposure. This project was supported by Project TRAIN (DBI-0602746), Project STEER (NIEHS R25ES016247-04) and RR017670.

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Apr 13th, 11:00 AM Apr 13th, 12:00 PM

SPARC and extracellular matrix production after asbestos exposure

UC Ballroom

Exposures to asbestos fibers by inhalation cause multiple asbestos-related diseases including asbestosis, lung cancer and mesothelioma. In asbestosis, the major consequence of asbestos exposure is increased extracellular matrix (ECM) production, primarily the deposition of collagen in the lungs. Previously our lab has shown that RNA expression of secreted protein acidic and rich in cysteine (SPARC) was increased in mouse lungs exposed to several types of asbestos fibers. SPARC is a matricellular protein involved in the regulation of ECM-cell interactions through modulation of growth factor activity. The central hypothesis to be tested in our studies is that the expression of SPARC is a significant step in the development of lung fibrosis through the modulation of ECM production. To test our hypothesis, we used expression of small interfering RNA (siRNA) to decrease SPARC production by facilitating the degradation of Sparc RNA. This was tested both in vitro with primary lung fibroblast cultures, as well as in vivo in a mouse model. Primary lung fibroblast cultures were established from C57Bl/6 mice and exposed to crocidolite asbestos to induce increased ECM production. Subsequently, the cultures were exposed to lentivirus containing siRNA sequences specifically designed to inhibit SPARC. Western blots will be performed to analyze SPARC and collagen production. Experiments are ongoing and current results will be presented. The ultimate goal of this project is to determine if control of SPARC expression has potential as a treatment for the fibrosis caused by asbestos exposure. This project was supported by Project TRAIN (DBI-0602746), Project STEER (NIEHS R25ES016247-04) and RR017670.