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Dissect the organ-specific cytotoxicity mechanism of streptokinase- streptodornase in canine cell lines

ABSTRACT: As streptokinase-streptodornase (SKD) can be used to treat respiratory diseases in dogs, we evaluated the cytotoxicity and related mechanisms of SKD in CF52.Tr and Madin–Darby canine kidney (MDCK) cells. The IC50 (half maximal inhibitory concentration) was observed at a concentration of 10 mg/mL of SKD in both cell lines. mRNA sequencing showed that SKD regulates 133 differentially expressed genes (DEGs) in CF52.Tr and 22 DEGs in MDCK (p<0.05, |log2 fold change| ≥ 1). The cytotoxicity induced by SKD in CF52.Tr cells are linked to increased inflammation and decreased cell cycle progression, as confirmed by the expression of cyclin-dependent kinases (CDKs). Furthermore, SKD-induced cytotoxicity in MDCK cells was associated with an increased cytoskeleton, as confirmed by the distribution of F-actin, and decreased cell cycle progression, as confirmed by cell cycle phase analysis. Notably, cell cycle progression in CF52.Tr is controlled by the transcription factor Forkhead box M1 (FoxM1). In summary, SKD-induced cell type-specific cytotoxicity is caused by the upregulation of inflammatory or cytoskeleton-related genes and the downregulation of cell cycle regulators.

ORGANISM(S): Canis lupus familiaris

PROVIDER: GSE302793 | GEO | 2025/12/31

REPOSITORIES: GEO

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