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. 2023 Jul 5;21:441. doi: 10.1186/s12967-023-04286-1

Fig. 3.

Fig. 3

Schematic pathway of the mitochondrial H2S and related protein in regulating ECs function and angiogenesis. Different colors of boxes indicate different locations of protein in cells listed on the left. H2S promoted angiogenesis by increasing cGMP production through activating eNOS/NO and prevention of cGMP breakdown through inhibiting phosphodiesterase (PDE), thus triggering cGMP/PKG-dependent downstream signaling such as ERK1/2 and p38 in case of angiogenesis. Silencing of CSE exacerbated mtROS production and decreased eNOS-NO production. Silencing CBS decreased transcription of VEGFR2 and neuropilin 1 (NRP1) by sulfhydration of specificity protein 1 (Sp1) at Cys68 and Cys755. Knockdown of 3-MST in ECs reduced VEGF-induced cell proliferation, migration, and tube-like network formation, inhibited mitochondrial oxidative phosphorylation. CBS: cystathionine beta-synthase; CSE: cystathionine-gamma-lyase; 3-MST: 3-mercaptopyruvate sulfurtransferase; SP1: specificity protein 1; PDE: phosphodiesterase; cGMP/PKG: cyclic guanosine 5′-monophosphate/protein kinase G; NRP1: neuropilin 1; CM: cell membrane; IMM: inner mitochondrial membrane