To Explore the Investigation in the Relevant Mechanism of Pten in Prolonged Low-Level Cadmium Exposure-Induced Nephrotoxicity in Rats

Abstract

Background: Chronic low-level cadmium exposure causes nephrotoxicity in rats. The microRNA-21 (miR-21) is highly expressed in cadmium-exposed rats. The aim of this study is to investigate the mechanism of miR-21 in regulation of Transforming Growth Factor-beta 1 (Tgf-β1)/Mothers Against Decapentaplegic Homolog (SMAD) Family Member 3 (Smad3) signaling through Phosphatase and Tensin Homolog (Pten) to cause nephrotoxicity of long-term low-level cadmium exposure in rats. Method: A rat model of long-term low-level cadmium exposure was established, and si-miR-21 lentivirus and Pten agonist (MT-141) were added for grouping. The serum and kidney tissues were extracted for pathological changes by Hematoxylin and eosin (HE) staining. The miR-21, Pten, Tgf-β1, and Smad3 were detected with PCR. Enzyme-linked immunosorbent assay (ELISA) was performed for Superoxide Dismutase (SOD), Malondialdehyde (MDA), Hydroxyproline (Hyp), Tumor Necrosis Factor-α (TNF-α), and Interleukin-10 (IL-10). The tissue apoptosis was observed by Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL). Results: The results proved that miR-21, Tgf-β1 and Smad3 were highly expressed in cadmium-exposed rats. After miR-21 inhibition, the Pten expression increased, while Tgf-β1 and Smad3 expression and oxidative stress decreased. After Pten activation, the expression of miR-21, Tgf-β1 and Smad3 decreased, which also inhibited nephrotoxicity in cadmium-exposed rats. Conclusions: Inhibition of miR-21 could ameliorate nephrotoxicity in rats caused by cadmium exposure, and the mechanism may be involved in the regulation of Pten.