{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T04:31:58Z","timestamp":1783398718614,"version":"3.54.6"},"reference-count":63,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T00:00:00Z","timestamp":1581379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>A prominent feature of obstructed tissue regeneration following injury in general, and fibrotic lung tissue in particular, is fibroblast proliferation and accumulation. The Fas\/FasL apoptotic pathway has been shown to be involved in human idiopathic pulmonary fibrosis (IPF) and bleomycin-induced lung fibrosis in rodents. We previously showed that in normal injury repair, myofibroblasts\u2019 accumulation is followed by their decline by FasL+ T cell-induced cell death. In pathological lung fibrosis, myofibroblasts resist cell death and accumulate. Like other members of the tumor necrosis factor (TNF) family, membrane-bound FasL can be cleaved from the cell surface to generate a soluble form (sFasL). Metalloproteinases (MMPs) are known to convert the membrane-bound form of FasL to sFasL. MMP-7 knockout (KO) mice were shown to be protected from bleomycin (BLM)-induced lung fibrosis. In this study, we detected increased levels of sFasL in their blood serum, as in the lungs of patients with IPF, and IPF-lung myofibroblast culture medium. In this study, using an MMP-inhibitor, we showed that sFasL is decreased in cultures of IPF-lung myofibroblasts and BLM-treated lung myofibroblasts, and in the blood serum of MMP-7KO mice. Moreover, resistant fibrotic-lung myofibroblasts, from the lungs of humans with IPF and of BLM-treated mice, became susceptible to T-cell induced cell death in a co-culture following MMP-inhibition- vs. control-treatment or BLM-treated MMP-7KO vs. wild-type mice, respectively. sFasL may be an unrecognized mechanism for MMP-7-mediated decreased tissue regeneration following injury and the evolution of lung fibrosis.<\/jats:p>","DOI":"10.3390\/cells9020411","type":"journal-article","created":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T11:45:30Z","timestamp":1581421530000},"page":"411","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Matrix Metalloproteinases Retain Soluble FasL-mediated Resistance to Cell Death in Fibrotic-Lung Myofibroblasts"],"prefix":"10.3390","volume":"9","author":[{"given":"David","family":"Nareznoi","sequence":"first","affiliation":[{"name":"Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine, Hadassah Medical Research Center, PO Box 12000, Kiryat Hadassah, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenya","family":"Konikov-Rozenman","sequence":"additional","affiliation":[{"name":"Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine, Hadassah Medical Research Center, PO Box 12000, Kiryat Hadassah, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmytro","family":"Petukhov","sequence":"additional","affiliation":[{"name":"Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine, Hadassah Medical Research Center, PO Box 12000, Kiryat Hadassah, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Breuer","sequence":"additional","affiliation":[{"name":"Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine, Hadassah Medical Research Center, PO Box 12000, Kiryat Hadassah, Jerusalem 91120, Israel"},{"name":"Department of Pathology and Laboratory Medicine, 670 Albany St, 4th Floor, Boston University School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shulamit B.","family":"Wallach-Dayan","sequence":"additional","affiliation":[{"name":"Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine, Hadassah Medical Research Center, PO Box 12000, Kiryat Hadassah, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1378\/chest.100.1.238","article-title":"Diagnostic Advances in Idiopathic Pulmonary Fibrosis","volume":"100","author":"King","year":"1991","journal-title":"Chest"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1378\/chest.108.2.297","article-title":"Idiopathic Pulmonary Fibrosis: Progress and Challenge","volume":"108","author":"Marinelli","year":"1995","journal-title":"Chest"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1164\/ajrccm.160.3.9903021","article-title":"A histologic pattern of nonspecific interstitial pneumonia is associated with a better prognosis than usual interstitial pneumonia in patients with cryptogenic fibrosing alveolitis","volume":"160","author":"Daniil","year":"1999","journal-title":"Am. 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