Protection of renal tubular epithelial cells from apoptosis by Cyr61 expression under hypoxia

Abstract

Acute kidney injury (AKI) is a common syndrome featuring the rapid loss of the kidney's excretory function, and presents a common and important diagnostic and therapeutic challenge for clinicians. There are no effective approaches to prevent and treat AKI. During early stage, most ischaemic AKI is reversible, so further research is essential for early intervention in order to prevent and reduce AKI. Cyr61 has been shown to be expressed in renal tubular cells in hypoxic-ischaemic kidney injury, whilst there is no expression in normal tubular cells. In the present study, we have established a stably Cyr61 expressed tubular cell line Cyr61-HK-2 based on HK-2 through recombinant Cyr61-lentivirus, and found that Cyr61 expression promotes tubular epithelial cell proliferation, while the cell apoptosis is inhibited. Further study demonstrated that Cyr61 expression led to BAD phosphorylation, which protects tubular cells from apoptosis, meanwhile Cyr61 activates the Akt and ERK signalling pathways, which are essential for cell proliferation. Altogether, our data showed the Cyr61 expression promotes cell proliferation, while dampening cell apoptosis under hypoxia, potentially suggesting a novel therapeutic approach for AKI.