Title

Can the Fibrotic Response of the Lungs to Asbestos Exposure be Mitigated Using Gene Knockdown?

Presentation Type

Presentation

Abstract

When someone is diagnosed with asbestosis (a chronic lung disease caused by inhaling asbestos fibers), there are few treatment options, none of which can halt or reverse the progression of the disease. The adverse health effects of asbestosis are due, in large part, to the response of the lungs to the asbestos fibers. Cells in the lungs deposit collagen around the fibers in an attempt to contain them, but this results in fibrosis and scaring of the lung tissue, making it difficult to breathe. In our studies we aimed to reduce the response of the lungs to the asbestos fibers using gene therapy techniques. If successful, this could offer a new avenue of potential therapy for those who have already been exposed to asbestos. A protein called SPARC (Secreted Protein Acidic and Rich in Cysteine) has been identified in previous studies as being important in the deposition of collagen and the fibrosis response. We interrupted the expression of this protein using a small interfering RNA molecule (siRNA) which we delivered via a viral vector. After identifying the most effective viral vectors in cells, we began our studies in mice. Mice in our study were first exposed to asbestos or a control solution and then, 2 months later, to our active virus or a control virus. After a month waiting period their lungs were analyzed: 1. histologically, to visually observe the presence of fibrosis, 2. Using RT-PCR to measure the presence of SPARC mRNA, 3. Using a Western Blot to measure the presence of collagen. If our results are consistent with our hypothesis, we will observe that the mice treated with active virus after asbestos exposure will experience less fibrosis and have less SPARC mRNA and less collagen in their lungs than the mice receiving the control virus.

Category

Life Sciences

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Apr 17th, 3:20 PM Apr 17th, 3:40 PM

Can the Fibrotic Response of the Lungs to Asbestos Exposure be Mitigated Using Gene Knockdown?

UC 332

When someone is diagnosed with asbestosis (a chronic lung disease caused by inhaling asbestos fibers), there are few treatment options, none of which can halt or reverse the progression of the disease. The adverse health effects of asbestosis are due, in large part, to the response of the lungs to the asbestos fibers. Cells in the lungs deposit collagen around the fibers in an attempt to contain them, but this results in fibrosis and scaring of the lung tissue, making it difficult to breathe. In our studies we aimed to reduce the response of the lungs to the asbestos fibers using gene therapy techniques. If successful, this could offer a new avenue of potential therapy for those who have already been exposed to asbestos. A protein called SPARC (Secreted Protein Acidic and Rich in Cysteine) has been identified in previous studies as being important in the deposition of collagen and the fibrosis response. We interrupted the expression of this protein using a small interfering RNA molecule (siRNA) which we delivered via a viral vector. After identifying the most effective viral vectors in cells, we began our studies in mice. Mice in our study were first exposed to asbestos or a control solution and then, 2 months later, to our active virus or a control virus. After a month waiting period their lungs were analyzed: 1. histologically, to visually observe the presence of fibrosis, 2. Using RT-PCR to measure the presence of SPARC mRNA, 3. Using a Western Blot to measure the presence of collagen. If our results are consistent with our hypothesis, we will observe that the mice treated with active virus after asbestos exposure will experience less fibrosis and have less SPARC mRNA and less collagen in their lungs than the mice receiving the control virus.