Fig. 9.

Proposed model of targeting succinate dehydrogenase of fibroblasts by IR-780 controls bleomycin induced lung fibrosis. Glycolysis upregulation and FAO downregulation contribute to lung fibrosis formation, and this process is caused by a significant accumulation of succinate in fibroblasts. IR-780, a near-infrared small molecule dye, as a targeting agent which stimulates mild inhibition of succinate dehydrogenase subunit A (SDHA) in normal fibroblasts, and which inhibits TGF-β1 induced SDH and succinate elevation, then to prevent fibrosis formation and respiratory dysfunction. Furthermore, enhanced cell retention of IR-780 at least partially mediating by SLCO4A1 is shown to promote severe inhibition of SDHA in myofibroblasts, which may contribute to excessive ROS generation and selectively induces myofibroblasts to apoptosis, and then therapeutically improves established lung fibrosis in vivo.