The Role of TPM3.1 in Regulating TAGLN-associated Stress Fibers During Lens Fibrosis

• Ashna Patel, Biological Sciences, University of Delaware

• Justin Parreno, Biological Sciences, University of Delaware

Fibrosis, a maladaptive wound-healing response, can lead to tissue damage and organ dysfunction. However, the earliest events that commit cells to become fibrotic are still not fully understood. Lens fibrosis after cataract surgery can lead to vision impairment due to epithelial to mesenchymal transition (EMT) of lens epithelial cells. During EMT, lens epithelial cells reorganize their actin cytoskeleton and develop αSMA-positive stress fibers, which contribute to cell contractility and fibrotic tissue remodeling. Previous work showed that αSMA-positive stress fibers consistently colocalized with TAGLN in immortalized mouse lens epithelial cells (imLECs). This suggests that TAGLN may help stabilize contractile stress fibers during fibrosis. It was also seen that Tropomyosin 3.1 (TPM3.1) is important for stress fiber formation during lens EMT. TPM3.1 has been associated with actin stress fibers, and inhibition of TPM3.1 using TR100 disrupted stress fiber formation and reduced fibrotic characteristics during TGFβ-induced EMT. Although TAGLN and TPM3.1 may both be involved in stress fiber formation, the relationship between them has not yet been studied. My project investigates whether TPM3.1 regulates TAGLN-associated αSMA-positive stress fibers during lens EMT. I will test whether inhibition of TPM3.1 using TR100 changes stress fiber formation and the localization of TAGLN and αSMA in imLECs during TGFβ2-induced EMT. This project may improve our understanding of lens fibrosis and help identify possible targets for preventing fibrotic complications after cataract surgery.