{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:25:14Z","timestamp":1787034314739,"version":"build-2736575974"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT 197809"],"award-info":[{"award-number":["PJT 197809"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>\n                    Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by inflammation, vasculopathy, and progressive fibrosis, yet the mechanisms underlying specific organ involvement are incompletely understood. Using the bleomycin\u2013osmotic minipump (BLM-MP) mouse model, which recapitulates key clinical and histopathological features of SSc, we investigated whether tissue-specific oxidative stress responses and BLM metabolism are associated with divergent inflammatory and fibrotic remodeling across organs. Male C57BL\/6 mice received continuous systemic infusion of BLM or saline for 7\u00a0days. Lungs, skin, kidneys, and liver were analyzed 14 and 28\u00a0days later by histopathology, collagen quantification, immunohistochemistry, and RT-qPCR. Systemic BLM exposure induced distinct organ-specific inflammatory, fibrotic and molecular responses. Progressive fibrosis and inflammatory infiltration developed predominantly in the lungs and skin, whereas the kidneys exhibited only mild focal cortical fibrosis and the liver remained largely unaffected. Fibrosis-prone organs displayed impaired antioxidant responses, characterized by reduced expression of superoxide dismutase 1 (\n                    <jats:italic>Sod1<\/jats:italic>\n                    ), glutathione peroxidase 3 (\n                    <jats:italic>Gpx3<\/jats:italic>\n                    ), and catalase (\n                    <jats:italic>Cat<\/jats:italic>\n                    ), together with decreased expression of bleomycin hydrolase (\n                    <jats:italic>Blmh<\/jats:italic>\n                    ), the enzyme responsible for BLM inactivation. In contrast, fibrosis-resistant organs exhibited preserved or increased expression of antioxidant enzymes and\n                    <jats:italic>Blmh<\/jats:italic>\n                    following BLM exposure, consistent with activation of protective redox and drug-clearance pathways. Across organs, lower antioxidant and\n                    <jats:italic>Blmh<\/jats:italic>\n                    expression was associated with greater inflammatory infiltration and collagen deposition. These findings identify a tissue-specific molecular signature with divergent inflammatory and fibrotic responses following systemic BLM exposure.\n                  <\/jats:p>","DOI":"10.3389\/fcell.2026.1888823","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:36:42Z","timestamp":1787031402000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Tissue-specific oxidative stress and bleomycin hydrolase signatures are associated with organ-specific fibrotic responses in a mouse model of systemic sclerosis"],"prefix":"10.3389","volume":"14","author":[{"given":"Rishabh","family":"Johri","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, McGill University","place":["Montreal, QC, Canada"]},{"name":"The Research Institute of the McGill University Health Centre (RI-MUHC)","place":["Montreal, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianela","family":"Brizio","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, McGill University","place":["Montreal, QC, Canada"]},{"name":"The Research Institute of the McGill University Health Centre (RI-MUHC)","place":["Montreal, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilien","family":"Lora","sequence":"additional","affiliation":[{"name":"The Research Institute of the McGill University Health Centre (RI-MUHC)","place":["Montreal, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney","family":"Joy","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, McGill University","place":["Montreal, QC, Canada"]},{"name":"The Research Institute of the McGill University Health Centre (RI-MUHC)","place":["Montreal, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Martin","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, McGill University","place":["Montreal, QC, Canada"]},{"name":"The Research Institute of the McGill University Health Centre (RI-MUHC)","place":["Montreal, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e9s","family":"Colmegna","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, McGill University","place":["Montreal, QC, Canada"]},{"name":"Division of Experimental Medicine, McGill University","place":["Montreal, QC, Canada"]},{"name":"The Research Institute of the McGill University Health Centre (RI-MUHC)","place":["Montreal, QC, Canada"]},{"name":"Division of Rheumatology, McGill University Health Centre","place":["Montreal, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.cotox.2018.08.001","article-title":"Oxidative toxicology of bleomycin: role of the extracellular redox environment","volume":"13","author":"Allawzi","year":"2019","journal-title":"Curr. 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