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Targeted apoptosis of myofibroblasts with the BH3 mimetic ABT-263 reverses established fibrosis
Open accessAbstract
with ABT-263 (navitoclax) effectively treats established fibrosis in a mouse model of scleroderma dermal fibrosis by inducing myofibroblast apoptosis. Using a BH3 profiling assay to assess mitochondrial priming in dermal fibroblasts derived from patients with scleroderma, we demonstrate that the extent of apoptosis induced by BH3 mimetic drugs correlates with the extent of their mitochondrial priming, indicating that BH3 profiling could predict apoptotic responses of fibroblasts to BH3 mimetic drugs in patients with scleroderma. Together, our findings elucidate the potential efficacy of targeting myofibroblast antiapoptotic proteins with BH3 mimetic drugs in scleroderma and other fibrotic diseases.
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“This increased stiffness is an important survival signal for myofibroblasts; via mechanosensing such stiffness results in intracellular activation of Rho and Rho-associated kinase (ROCK) whose activity increases BCL2-XL expression (36).”
From Unraveling SSc Pathophysiology; The Myofibroblast (2018) · cites this paper as [36]
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“Recently, it has been shown that pharmacological inhibition of BCL2-XL can mimic this process and induce targeted BIM-mediated apoptosis in myofibroblasts and even revert established (murine) fibrosis (36).”
From Unraveling SSc Pathophysiology; The Myofibroblast (2018) · cites this paper as [36]
In the citing paper
“Importantly, this increased, stiffness-induced, BCL2-XL expression is needed to counteract the function of the pro-apoptotic protein BIM (36). BIM is an activator of BAX and accumulates in myofibroblasts exposed to a stiff matrix. This accumulation primes the cells to undergo apoptosis (36), and only the continued presence of BCL2-XL prevents this.”
From Unraveling SSc Pathophysiology; The Myofibroblast (2018) · cites this paper as [36]
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Cites
Gurtner, G. C., Werner, S., Barrandon, Y., & Longaker, M. T. (2008) · Nature · doi:10.1038/nature07039 · Cited by 6,542
Role of YAP/TAZ in mechanotransduction
Dupont, S., Morsut, L., Aragona, M., Enzo, E., Giulitti, S., Cordenonsi, M., Zanconato, F., Le Digabel, J., Forcato, M., Bicciato, S., et al. (2011) · Nature · doi:10.1038/nature10137 · Cited by 5,979
The BCL-2 protein family: opposing activities that mediate cell death
Youle, R. J., & Strasser, A. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2308 · Cited by 4,806
Mechanisms of fibrosis: therapeutic translation for fibrotic disease
Wynn, T. A., & Ramalingam, T. R. (2012) · Nature Medicine · doi:10.1038/nm.2807 · Cited by 3,541
An inhibitor of Bcl-2 family proteins induces regression of solid tumours
Oltersdorf, T., Elmore, S. W., Shoemaker, A. R., Armstrong, R. C., Augeri, D. J., Belli, B., Bruncko, M., Deckwerth, T. L., Dinges, J., Hajduk, P. J., et al. (2005) · Nature · doi:10.1038/nature03579 · Cited by 3,407
Self-citationControl of apoptosis by the BCL-2 protein family: implications for physiology and therapy
Czabotar, P. E., Lessene, G., Strasser, A., & Adams, J. M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3722 · Cited by 3,219
ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets
Souers, A. J., Leverson, J. D., Boghaert, E. R., Ackler, S. L., Catron, N. D., Chen, J., Dayton, B. D., Ding, H., Enschede, S. H., Fairbrother, W. J., et al. (2013) · Nature Medicine · doi:10.1038/nm.3048 · Cited by 3,058
Hinz, B., Phan, S. H., Thannickal, V. J., Galli, A., Bochaton-Piallat, M.-L., & Gabbiani, G. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.070112 · Cited by 2,068
ABT-263: A Potent and Orally Bioavailable Bcl-2 Family Inhibitor
Tse, C., Shoemaker, A. R., Adickes, J., Anderson, M. G., Chen, J., Jin, S., Johnson, E. F., Marsh, K. C., Mitten, M. J., Nimmer, P., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5836 · Cited by 1,992
Fibrosis–a common pathway to organ injury and failure
Rockey, D. C., Bell, P. D., & Hill, J. A. (2015) · New England Journal of Medicine · doi:10.1056/nejmra1300575 · Cited by 1,428
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Items 201–246 of 246
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Dill, M. N., Turner, Z. R., Kapuscinska, P. W., Heiden, K. D., Basso, K. B. G., Simmons, C. S., & Moore, E. (2025) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.5c00810 · Cited by 1
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Tanner, L., Bergwik, J., Bhongir, R. K. V., & Egesten, A. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.12.01.470755 · Cited by 1
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Ocon, A. J., Lokineni, S., & Korman, B. D. (2022) · Current Treatment Options in Rheumatology · doi:10.1007/s40674-021-00189-8
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Shiraishi, M., Suzuki, K., & Yamaguchi, A. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.11.05.515315
Fletcher-Sananikone, E., Kanji, S., Tomimatsu, N., Cristofaro, L. F. M. D., Kollipara, R. K., Saha, D., Floyd, J., Sung, P., Hromas, R., Burns, T. C., et al. (2023) · doi:10.1158/0008-5472.c.6513888.v1
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Khatri, S., Bustos, A. H., Jørgensen, C. D., Torok, K. S., Gjerdrum, L. M. R., & Astakhova, K. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242417507
Owuor, J. O., & Soubani, A. O. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15500-0.00020-7
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Santos, A., Islam, T., Chrysovergi, M.-A., Grasberger, P. E., Auernheimer, V., Al-Hilal, T. A., Lamas, S., & Lagares, D. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.20.682962
Self-citationZhao, T., He, Q., Xie, S., Zhan, H., Jiang, C., Lin, S., Liu, F., Wang, C., Chen, G., & Zeng, H. (2023) · Figshare · doi:10.6084/m9.figshare.22603577
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Martini, H. (2019) · theses.fr (ABES) · doi:10.70675/bb7ddcb3z0b6az4c39za6eczc94e0563f0a3
Louault, K. (2018) · theses.fr (ABES) · doi:10.70675/0aef1137z5689z4922z8455zdbe4b757612c
Maurya, R. K., Sharma, A. K., Schaefbauer, K. J., Ma, L., Koenitzer, J. R., LIMPER, A. H., & Choudhury, M. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.01.715935
Feng, C., Liu, Y., Zhang, C., Niu, L., Dong, J., & Wang, B. (2026) · Drug Delivery and Translational Research · doi:10.1007/s13346-026-02120-x
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Shu, F., Huang, H., Sun, H., Fang, Z., Wu, W., Zhou, Z., Sheng, C., Liu, H., Xiao, S., Wu, S., et al. (2026) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.6c03628
Tian, Y., Yang, Y., Li, Q., Hu, Y., Hu, Q., Ran, S., Zhou, S., Yang, X., Li, S., & Zhang, Q. (2026) · Advanced Science · doi:10.1002/advs.75850 · Cited by 1
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Karimi, M. Y., & Colagar, A. H. (2026) · Oxidative Medicine and Cellular Longevity · doi:10.1155/omcl/5547254
Yu, H., Li, M., Kang, X., Dai, Y., Li, F., Zhang, Y., & Li, Q. (2026) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2026.120558
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Lazebnik, T., & Friedman, A. (2026) · Bulletin of Mathematical Biology · doi:10.1007/s11538-026-01700-9
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Thangaraju, R., Kamlesh, N., Shipin, M., Mitra, T., Kumar, A. H. S. A., Gopinathan, A., Ansari, A. P., Karwasra, R., Karthikeyan, D., Agrawal, P., et al. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1816025
Tennant, F., & Gilmore, A. P. (2026) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2026.103693
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Song, Y., Wang, S., Darjatmoko, S. R., Sheibani, N., & Sorenson, C. M. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27167455
Wang, Y., Liu, Q., Li, X., Tan, R., Li, H., Fan, J., Zhu, J., & Wang, L. (2026) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-026-05972-9
Randall, L. J., Tran, T. D., Siddals, G., Harvey, V. L., Greensill, A., Woodhill, K. E., & Russell, F. D. (2026) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-026-05771-z
Rood, B. R., Hodges, E. R., Gao, Y., Słomnicki, Ł. P., Armstrong, C. A., Andres, K. R., Chariker, J. H., Rouchka, E. C., Ohri, S. S., & Hetman, M. (2026) · Neurotrauma Reports · doi:10.1177/2689288x261499234
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Infantino, V., Todisco, S., & Convertini, P. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-45078-5.00018-x
Whaley, M. G., Saraf, N., Chow, D., Riley, S. G., Vu, J. A., Bringhurst, M. F., Li, P., Bakri, S. J., & Haak, A. J. (2026) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/j.jpet.2026.105045
Metadata
- Authors
- Lagares, D., Santos, A., Grasberger, P. E., Liu, F., Probst, C. K., Rahimi, R. A., Sakai, N., Kuehl, T., Ryan, J., Bhola, P., Montero, J., Kapoor, M., Baron, M., Varelas, X., Tschumperlin, D. J., Letai, A., & Tager, A. M.
- Affiliations
- Harvard University (US)
- Fibrosis Research Center and Center for Immunology and Inflammatory Diseases, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
- University Health Network (CA)
- Jewish General Hospital (CA)
- Boston University (US)
- Mayo Clinic (US)
- Corresponding author
- Lagares, David
- Santos, Alba
- Grasberger, Paula E.
- Tager, Andrew M.
- ORCID
- Venue
- Science Translational Medicine
- Published
- 2017-12-13
- Volume
- 9
- Issue
- 420
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC8520471
- OpenAlex
- W2774171294
- Cited by
- 246
- References
- 63
- Citations by year
- 2026: 31 · 2025: 25 · 2024: 30 · 2023: 36 · 2022: 21 · 2021: 34 · 2020: 28 · 2019: 23 · 2018: 17 · 2017: 1
- FWCI
- 14.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (2r01hl092961-13)
- National Heart, Lung, and Blood Institute (R01-HL-092961, R01HL108975, K08HL140173)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Sclerosis and Related Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- navitoclax, BH3 mimetics, myofibroblast apoptosis, systemic sclerosis, skin fibrosis, fibrosis reversal, mitochondrial priming, BH3 profiling, anti-apoptotic proteins, drug response prediction
- MeSH terms
- Aniline Compounds, Animals, Biomechanical Phenomena, Cell Survival, Disease Models, Animal, Extracellular Matrix, Fibrosis, Humans, Male, Mice, Inbred C57BL, Mitochondria, Scleroderma, Systemic, Sulfonamides, Signal Transduction, Apoptosis, Dermis, Mechanotransduction, Cellular, bcl-X Protein, Mitochondrial Membranes, Myofibroblasts
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