Nestin Improves Preeclampsia-Like Symptoms by Inhibiting Activity of Cyclin-Dependent Kinase 5

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder that is characterised by a high incidence of hypertension and proteinuria. Podocytes are involved in the formation of a split membrane, which is the last barrier preventing the leakage of protein into the urine. Nestin, a cytoskeleton protein, is expressed stably in podocytes. However, the association between the Nestin concentration in urine and the progression of PE and the role of Nestin in PE remains unclear.

In the present study, a mouse podocyte cell line, PE-like animal model and PE patients' urine samples were used. Eilsa kits were used to detect the levels of proteins expression in urine samples from patients and animal models. Western Blotting and immunofluorescence were used to detect proteins expression levels in cell samples and animal tissue samples. Flow cytometry was used to detect the level of apoptosis in cells. Tunel assay was used to detect the levels of apoptosis in animal tissue samples.

Nestin levels were significantly increased in PE patients than in hypertensive patients and healthy subjects, and positively correlated with proteinuria and podocalyxin. Ang II treatment decreased the expression of Nestin and Podocin in a time- and dose- dependent manner in podocytes. Restoration of the Nestin levels could reverse Ang II-induced F-actin degradation and attenuate Ang II-mediated podocyte apoptosis, while knockdown of the Nestin level exhibited the opposite. Moreover, the protective role of Nestin on podocytes is mediated by inhibition of the kinase activity of CDK5. In PE-like animal model induced by L-NAME injection, restoration of Nestin lowered the pressure and proteinuria concentration, attenuated the loss of podocytes, and decreased the expression of p35, p53 and the activity of CDK5 kinase, as compared with the control.

Our findings suggest that Nestin could improve preeclampsia-like symptoms by inhibiting the activity of CDK5, and Nestin may become a new prognostic factor and a potential therapy target for PE.