Differential Gene Expression in Capsules from Textured versus Smooth Silicone Implants
Daniel J. Gardner, MS, Annie Chen, BS, Soleil Niknam-Bienia, MD, Vinaya Soundararajan, BS, Maxwell B. Johnson, MS, Athanasios Bramos, MD, Alex K. Wong, MD.
Keck School of Medicine of USC, Los Angeles, CA, USA.
Capsular contracture complicates implant-based breast surgery leading to abnormal appearance, increased firmness, and pain to touch. It is known that textured implants reduce the rate of capsular contracture. This study examines RNA expression in a rat model of capsular formation around textured and smooth silicone implants in order to understand contracture pathogenesis and identify therapeutic targets.
Miniature round smooth or textured silicone devices were implanted into a subcutaneous flank pocket of Fisher rats (n=10). After 6 weeks, the capsule was explanted and examined by histological and molecular techniques. Differential gene expression was identified using RNA sequencing. Selected gene expression levels were confirmed by quantitative RTPCR and IHC.
RNA sequencing data were subjected to the Probability of Positive Log Ratio (PPLR) algorithm. Transcripts were identified for further characterization using cutoff values of PPLR >= 0.975 (2-fold increase) or a PPLR <= 0.025 (2-fold decrease). We identified 18,555 transcripts, and 404 transcripts met PPLR inclusion criteria. Quantitative real-time PCR (RT-PCR) was performed for matrix metalloproteinase 3 (MMP3), troponin 3 (TNNT3), and neuregulin 1 (NRG1). MMP3 and TNNT3 are downregulated in smooth implant capsules with a fold difference of -2.04 (p=<0.006) and -3.03 (p=<0.0056), respectively. NRG1 is upregulated in smooth implant capsules with a fold difference of +2.65 (p=<0.0001). IHC staining was consistent with differential expression patterns.
We demonstrate that capsules around smooth and textured implants have different histological appearances and different patterns of gene expression. These differences may explain the decreased rate of contractures seen surrounding textured implants.
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