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  • Inhibiting Fibroblast Mechanotransduction Modulates Severity of Idiopathic Pulmonary Fibrosis. Advances in wound care Trotsyuk, A. A., Chen, K., Kwon, S. H., Ma, K. C., Henn, D., Mermin-Bunnell, A. M., Mittal, S., Padmanabhan, J., Larson, M. R., Steele, S. R., Sivaraj, D., Bonham, C. A., Noishiki, C., Rodrigues, M., Jiang, Y., Jing, S., Niu, S., Chattopadhyay, A., Perrault, D. P., Leeolou, M. C., Fischer, K., Gurusankar, G., Choi Kussie, H., Wan, D. C., Januszyk, M., Longaker, M. T., Gurtner, G. C. 2021

    Abstract

    OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that affects 63 in every 100,000 Americans. Its etiology remains unknown, although inflammatory pathways appear to be important. Given the dynamic environment of the lung, we examined the significance of mechanotransduction on both inflammatory and fibrotic signaling during IPF.INNOVATION: Mechanotransduction pathways have not been thoroughly examined in the context of lung disease and pharmacologic approaches for IPF do not currently target these pathways. The interplay between mechanical strain and inflammation in pulmonary fibrosis remain incompletely understood.APPROACH: In this study, we used conditional KO mice to block mechanotransduction by knocking out FAK (Focal Adhesion Kinase) expression in fibroblasts, followed by induction of pulmonary fibrosis using bleomycin. We examined both normal human and human IPF fibroblasts and used immunohistochemistry, qRT-PCR, and Western Blot to evaluate the effects of FAK inhibition (FAKI) on modulating fibrotic and inflammatory genes.RESULTS: Our data indicate that deletion of FAK in mice reduces expression of fibrotic and inflammatory genes in lungs. Similarly, mechanical straining in normal human lung fibroblasts activates inflammatory and fibrotic pathways. FAK inhibition decreases these signals but has less effect on IPF fibroblasts as compared to normal human fibroblasts.CONCLUSION: Administering FAKI at early stages of fibrosis may attenuate the FAK-mediated fibrotic response pathway in IPF, potentially mediating disease progression.

    View details for DOI 10.1089/wound.2021.0077

    View details for PubMedID 34544267

  • First reported case of Wohlfahrtiimonas chitiniclastica infection in California JAAD Case Reports Journal of the American Academy of Dermatology Case Reports Leelou, M. C., Perrault, D. P., Siravaj, D., Chang, A. S., Chen, K., Trotsyuk, A., Padmanabhan, J., Gurtner, G. C. 2021