BAICALIN INHIBITS CELL APOPTOSIS, INFLAMMATION, AND FERROPTOSIS IN ULCERATIVE COLITIS BY INFLUENCING SP1-MEDIATED TRANSCRIPTION OF SLC6A14.

Background

Baicalin is considered to be able to alleviate the progression of ulcerative colitis (UC), but the underlying molecular mechanism needs to be further elucidated.

Methods

TNF-α-induced human normal colorectal mucosa cells (FHC) were used to mimic UC models in vitro , and trinitrobenzene sulfonic acid (TNBS)-injected rats were used to construct UC models in vivo . Cell proliferation and apoptosis were determined by CCK8 assay, EdU assay and flow cytometry. Inflammation factors were examined by ELISA, and ferroptosis-related markers were detected by corresponding kit. The mRNA and protein levels of solute carrier family 6 member 14 (SLC6A14) and specific protein 1 (SP1) were analyzed by qRT-PCR and western blot. The interaction between SP1 and SLC6A14 promoter was verified by ChIP assay and dual-luciferase reporter assay.

Results

Baicalin enhanced proliferation, while repressed apoptosis, inflammation, and ferroptosis in TNF-α-induced FHC cells. SLC6A14 was upregulated in UC patients, and baicalin could decrease SLC6A14 expression. SLC6A14 overexpression reversed the inhibitory effect of baicalin on TNF-α-induced FHC cell injury. SP1 could bind to SLC6A14 promoter region to upregulate its expression, and ectopic expression of SLC6A14 also abolished the suppressive effect of SP1 knockdown on TNF-α-induced FHC cell injury. Baicalin reduced SP1 expression to downregulate SLC6A14. In addition, baicalin alleviated UC process in vivo via repressing inflammation, and ferroptosis.

Conclusion

Baicalin repressed SP1-mediated transcription of SLC6A14 to restrain cell apoptosis, inflammation, and ferroptosis, thus alleviating UC progression.