Loxigen

Fibrosis

Fibrosis

Lysyl oxidase family proteins have been recognized as having key roles in fibrogenesis1-3 and suggested to be attractive targets for antifibrotic treatment4. Inhibition of lysyl oxidase activity alleviates fibrosis by reducing fibrillar collagen cross-linking, thus potentially impeding the formation of Idiopathic pulmonary fibrosis (IPF)4-6. Furthermore, our analyses revealed that 70-75% of the lung fibrosis patients are high LOX-expressing compared to normal lung, thus proving the high therapeutic potential of targeting lysyl oxidase enzymes for treatment of pulmonary fibrosis.

Refrences

  1. Hewitt, R.J., Puttur, F., Gaboriau, D.C.A., Fercoq, F., Fresquet, M., Traves, W.J., et al. Lung extracellular matrix modulates KRT5(+) basal cell activity in pulmonary fibrosis. Nat Commun 2023;14:6039.
  2. Chaudhari, N., Findlay, A. D., Stevenson, A. W., Clemons, T. D., Yao, Y., Joshi, A., et al. Topical application of an irreversible small molecule inhibitor of lysyl oxidases ameliorates skin scarring and fibrosis. Nat Commun 2022;13(1):5555
  3. Klepfish, M., Gross, T., Vugman, M., Afratis, N.A., Havusha-Laufer, S., Brazowski, E., et al. LOXL2 Inhibition Paves the Way for Macrophage-Mediated Collagen Degradation in Liver Fibrosis. Front Immunol 2020;11:480.
  4. Schilter, H., Findlay, A. D., Perryman, L., Yow, T. T., Moses, J., Zahoor, A., et al. The lysyl oxidase like 2/3 enzymatic inhibitor, PXS-5153A, reduces crosslinks and ameliorates fibrosis. J Cell Mol Med 2019;23(3):1759-1770.
  5. Chen, L., Li, S.,Li, W. LOX/LOXL in pulmonary fibrosis: potential therapeutic targets. J Drug Target 2019;27:790-796.
  6. Wen, X., Liu, Y., Bai, Y., Li, M., Fu, Q.,Zheng, Y. LOXL2, a copper-dependent monoamine oxidase, activates lung fibroblasts through the TGF-beta/Smad pathway. Int J Mol Med 2018;42:3530-3541.
  7. Yang, J., Savvatis, K., Kang, J.S., Fan, P., Zhong, H., Schwartz, K., et al. Targeting LOXL2 for cardiac interstitial fibrosis and heart failure treatment. Nat Commun 2016:7:13710.