To investigate the alteration of protein phosphorylation of signaling pathways and the role of connexin 43 (Cx43) in human renal proximal tubular cells following cadmium (CdCl₂) treatment.

Human renal proximal tubular cell lines (HK-2) were exposed to 1 μmol/L CdCl₂ for 10 days. Cx43 was silenced by RNA interference technique (siRNA). Western blot was used to detect protein expression of Cx43. The protein phosphorylation of signaling pathways was determined by phosphor explorer antibody array.

After HK-2 cells exposed to CdCl₂ for 10 days, 61 phosphorylation proteins were altered, belonging to ErbB, mitogen-activated protein kinase (MAPK), T cells receptor, and B cells receptor signaling pathways. Decreased proliferation (P < 0.05) and elevated apoptosis (P < 0.05) in HK-2 cells were observed. After Cx43 was silenced prior to the exposure, 56 phosphorylation proteins were altered when compared with the control group, which belonged to Focal adhesion, ErbB, and MAPK signaling pathways. However, apoptosis did not change (P>0.05) with decreased cell proliferation (P < 0.05). Compared with the CdCl₂ exposure group, 102 altered phosphorylation proteins involved in Focal adhesion, ErbB, MAPK, Apoptosis, and Chemokine signaling pathways were identified with decreased apoptosis (P < 0.05) and no change in cell proliferation (P>0.05) in the Cx43 silencing posterior to CdCl₂ exposure group.

An extended cadmium exposure of HK-2 cells could decrease cell proliferation, increase apoptosis, and affect ErbB, MAPK, T cells receptor, and B cells receptor signaling pathways. Down-regulated expression of Cx43 may regulate the proliferation and apoptosis of cells by changing the protein phosphorylation of signaling pathways such as Focal adhesion, ErbB, MAPK, Apoptosis, and Chemokine.