The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Inhibition of mechanosensitive signaling in myofibroblasts ameliorates experimental pulmonary fibrosis
Open accessAbstract
Matrix stiffening and myofibroblast resistance to apoptosis are cardinal features of chronic fibrotic diseases involving diverse organ systems. The interactions between altered tissue biomechanics and cellular signaling that sustain progressive fibrosis are not well defined. In this study, we used ex vivo and in vivo approaches to define a mechanotransduction pathway involving Rho/Rho kinase (Rho/ROCK), actin cytoskeletal remodeling, and a mechanosensitive transcription factor, megakaryoblastic leukemia 1 (MKL1), that coordinately regulate myofibroblast differentiation and survival. Both in an experimental mouse model of lung fibrosis and in human subjects with idiopathic pulmonary fibrosis (IPF), we observed activation of the Rho/ROCK pathway, enhanced actin cytoskeletal polymerization, and MKL1 cytoplasmic-nuclear shuttling. Pharmacologic disruption of this mechanotransduction pathway with the ROCK inhibitor fasudil induced myofibroblast apoptosis through a mechanism involving downregulation of BCL-2 and activation of the intrinsic mitochondrial apoptotic pathway. Treatment with fasudil during the postinflammatory fibrotic phase of lung injury or genetic ablation of Mkl1 protected mice from experimental lung fibrosis. These studies indicate that targeting mechanosensitive signaling in myofibroblasts to trigger the intrinsic apoptosis pathway may be an effective approach for treatment of fibrotic disorders.
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Cites
Myofibroblasts and mechano-regulation of connective tissue remodelling
Tomasek, J. J., Gabbiani, G., Hinz, B., Chaponnier, C., & Brown, R. A. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm809 · Cited by 4,290
Mechanisms of fibrosis: therapeutic translation for fibrotic disease
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Senescence of Activated Stellate Cells Limits Liver Fibrosis
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Myofibroblast contraction activates latent TGF-β1 from the extracellular matrix
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Latent TGF-β structure and activation
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Perspective Article: Tissue repair, contraction, and the myofibroblast
Desmoulière, A., Chaponnier, C., & Gabbiani, G. (2005) · Wound Repair and Regeneration · doi:10.1111/j.1067-1927.2005.130102.x · Cited by 892
Matrix stiffness-induced myofibroblast differentiation is mediated by intrinsic mechanotransduction
Huang, X., Yang, N., Fiore, V. F., Barker, T. H., Sun, Y., Morris, S. W., Ding, Q., Thannickal, V. J., & Zhou, Y. (2012) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2012-0050oc · Cited by 530
Self-citationHinz, B. (2009) · Current Rheumatology Reports · doi:10.1007/s11926-009-0017-1 · Cited by 373
Cited by
Richeldi, L., Collard, H. R., & Jones, M. G. (2017) · The Lancet · doi:10.1016/s0140-6736(17)30866-8 · Cited by 2,020
Mechanosignaling through YAP and TAZ drives fibroblast activation and fibrosis
Liu, F., Lagares, D., Choi, K. M., Stopfer, L., Marinković, A., Vrbanac, V., Probst, C. K., Hiemer, S. E., Sisson, T. H., Horowitz, J. C., et al. (2015) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00300.2014 · Cited by 874
The extracellular matrix and transforming growth factor-β1: Tale of a strained relationship
Hinz, B. (2015) · Matrix Biology · doi:10.1016/j.matbio.2015.05.006 · Cited by 608
Glycolytic Reprogramming in Myofibroblast Differentiation and Lung Fibrosis
Xie, N., Tan, Z., Banerjee, S., Cui, H., Ge, J., Liu, R.-M., Bernard, K., Thannickal, V. J., & Liu, G. (2015) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201504-0780oc · Cited by 582
Self-citationBurgstaller, G., Oehrle, B., Gerckens, M., White, E. S., Schiller, H. B., & Eickelberg, O. (2017) · European Respiratory Journal · doi:10.1183/13993003.01805-2016 · Cited by 482
Metadata
- Authors
- Zhou, Y., Huang, X., Hecker, L., Kurundkar, D., Kurundkar, A., Liu, H., Jin, T.-H., Desai, L., Bernard, K., & Thannickal, V. J.
- Venue
- Journal of Clinical Investigation
- Published
- 2013-02-22
- Volume
- 123
- Issue
- 3
- Pages
- 1096-1108
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2004107033
- Cited by
- 455
- References
- 9
- FWCI
- 31.42
- Type
- journal article
- Language
- en
- Open access
- green
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- Zhou, Y., Huang, X., Hecker, L., Kurundkar, D., Kurundkar, A., Liu, H., Jin, T.-H., Desai, L., Bernard, K., & Thannickal, V. J. (2013). Inhibition of mechanosensitive signaling in myofibroblasts ameliorates experimental pulmonary fibrosis. Journal of Clinical Investigation. https://doi.org/10.1172/jci66700
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