Regulation of TGF-β1-Mediated Wnt/β-catenin Pathways Plays an Important Role in EMT-like Transformation Induced by Cadmium

Abstract

Backgrounds Some studies have reported that different dosage of cadmium (Cd) had a biphasic effect on cells viability, Cd at a dose of more than 20 μM can induce excessive apoptosis which past studies were mainly concentrated on while there has been few reports on a relatively lower dose of Cd causing abnormal proliferation. Kidney is the most sensitive target organ of Cd, however, the mechanism how Cd at a relatively lower dose affects the proliferation of renal tubular epithelial cells (RTEC) is not yet clear at present. Objectives To explore the toxic effect of Cd at a relatively lower dose on RTEC and study the mechanism how the TGF-β1-mediated Wnt/β-catenin pathways involved in EMT-like transformation induced by Cadmium. Methods The RTEC were isolated by mixed collagenase digestion methods and the effect of Cd at different dose on cell viability was detected by MTT assay. The effect of Cd at Hormesis zone dose on the expression of c-myc, cyclinD1, α-SMA, TGF-β1, Wnt and β-catenin were determined by qRT-PCR. Results When exposed for 24h-72h, Cd at a dose of 2.5 μM had maximum proliferation promoting effect. Cd at Hormesis zone dose could up-regulate the expression of cell cycle and proliferation key regulators c-myc and cyclinD1 in an obvious time-dependent manner. Cd at Hormesis zone dose could significantly promote α-SMA, TGF-β1, Wnt and β-catenin mRNA expression. Conclusions Cd at Hormesis zone dose could induce RTEC significant abnormal proliferation and EMT-like transformation. The activation of TGF-β1-mediated Wnt/β-catenin pathways might play a key role in EMT-like transformation induced by Cd at Hormesis zone dose.