Abstract 12779: Up-Regulation of the Renal Sodium Transporters is Associated With Increased CD81 in Preeclampsia Rats and Patients

Abstract

Introduction: the abnormalities of placental CD81 play an important role in preeclampsia (PE), a disorder that links to the impaired placentation in the early stages of pregnancy and the subsequent systemic endothelial cell activation. Hypothesis: up-regulation of the renal sodium transporters is associated with increased CD81 in preeclampsia rats and patients Methods: we examined the renal protein abundance of CD81 and sodium transporters, channels and pump along nephron in rat model with lipopolysaccharide (LPS) -induced PE. A single ultra-low dose of LPS (0.5ug/kg) (PE) or vehicle(control group,CTL) were applied to female SD rats( age: 8-12 wks, n=4/group) on gestational day 5 (GD5) by intraperitoneal injection. Results: The SBP (101±1.6 vs 116±0.8 mmHg, p<0.001, tail-cuff, BP-98A, Softron, Japan) and urine albumin (1885±35 vs 3550±157.8 ug, p<0.001) were higher in PE than CTL while there were no differences in BW, fetus number/weight and serum creatinine and cholesterol concentrations (GD18) between the 2 groups. The renal protein abundances of NKCC2 (168±14 vs 100±13, % of control,P=0.02,immunoblotting) and NCC (161±16 vs 100±13, P=0.04) , among the 8 sodium transport proteins checked, were greater in PE group than in CTL group along with the increase in renal protein abundances of CD81 in PE group relative to CTL group. The protein expressions of MCP-1, IL-6, TNF-a were similar between the 2 groups. CD81 were located in thick ascending limbs of Henle’s loop and distal convoluted tubules and co-immunoprecipitated with NKCC2 and NCC in rat homogenates. CD81 was not altered in placenta, serum, liver in the LPS-PE model indicated that the increase of CD81 is kidney-specific. In PE patients , urinary exosome CD81 was also increased along with increases of NKCC2 and NCC. Furthermore, the increases of CD81 and NCC were confirmed in cultured mouse distal convoluted tubule cells (DCT) stimulated by LPS for 24 hrs at different concentrations. The knockdown of CD81 by siRNA for 48 hrs had no effects on NCC but blocked the increase of NCC induced by LPS for 24 hr. Conclusions: inhibition and decrease of renal CD81 may reverse the increases of renal sodium transporters, therefore improve the hypertension in preeclampsia.