Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

TRIM8 regulates contrast-induced renal cell injury via the TLR4/MyD88/ NF-κB pathway

Weigang Li, Lili Su², Jian Zhang¹

¹Department of Imaging, Taizhou People's Hospital, 366 Taihu Road, Pharmaceutical High-tech Zone, Taizhou 225300, China; ²Department of Nursing, Taizhou People's Hospital, 366 Taihu Road, Pharmaceutical High-tech Zone, Taizhou 225300, China.

For correspondence:- Jian Zhang Email: 350130302@qq.com Tel:+8615052309755

Accepted: 16 December 2022 Published: 30 January 2023

Citation: Li W, Su L, Zhang J. TRIM8 regulates contrast-induced renal cell injury via the TLR4/MyD88/ NF-κB pathway. Trop J Pharm Res 2023; 22(1):23-30 doi: 10.4314/tjpr.v22i1.4

© 2023 The authors.
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Abstract

Purpose: To investigate the effect of tripartite motif-containing protein 8 (TRIM8) on contrast media-induced injury on kidneys in mice and on human renal tubular epithelial cells.

Methods: Contrast media-induced nephropathy (CIN) model was constructed by injecting meglumine diatrizoate in mice. Small interference technology was used to knock down the expression of TRIM8 in HK-2 cells, while quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to determine the expression levels of the inflammatory factors: TNF-α, TGF-β1, IL-1β, and IL-4. Cell counting kit-8 (CCK-8) assay was employed to determine the cell viability of each group, and TUNEL staining applied to detect apoptosis morphology using a fluorescence microscope. Flow-type Annexin V-FITC/PI double staining and Caspase-3 activity colorimetry were used to observe the changes in apoptosis. expression of apoptosis factors, including Bax, Caspase3, Caspase9, and anti-apoptotic factor Bcl-2, was determined by qRT-PCR, while expressions of the TLR4/MyD88/NF-kB pathway were determined using Western blot and qRT-PCR.

Results: In CIN group, the kidney tissues significantly expressed IL-1β and Caspase3, while the contents of BUN, SCr, and UP all increased (p < 0.05). At the same time, expression of TRIM8 in the kidney tissues was up-regulated. After knocking down TRIM8, HK-2 cells inhibited the contrast agent-induced apoptosis and inflammation and as well as TLR4/MyD88/NF-kB pathway (p < 0.05).

Conclusion: TRIM8 regulates contrast-induced renal cell damage via TLR4/MyD88/NF-KB pathway. The results of the current study may provide new insights for the development of new treatment strategies for CIN.

Keywords: Contrast-media induced nephropathy, Tripartite motif-containing protein 8, Inflammation, Apoptosis, TLR4/MyD88/NF-kB pathway