Tissue-specific oxidative stress and bleomycin hydrolase signatures are associated with organ-specific fibrotic responses in a mouse model of systemic sclerosis.

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-osmotic 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 days. Lungs, skin, kidneys, and liver were analyzed 14 and 28 days 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 (