PMID- 36961378 OWN - NLM STAT- MEDLINE DCOM- 20230328 LR - 20230407 IS - 1530-6860 (Electronic) IS - 0892-6638 (Linking) VI - 37 IP - 4 DP - 2023 Apr TI - Renal CD81 interacts with sodium potassium 2 chloride cotransporter and sodium chloride cotransporter in rats with lipopolysaccharide-induced preeclampsia. PG - e22834 LID - 10.1096/fj.202201546RR [doi] AB - The kidney regulates blood pressure through salt/water reabsorption affected by tubular sodium transporters. Expanding our prior research on placental cluster of differentiation 81 (CD81), this study explores the interaction of renal CD81 with sodium transporters in preeclampsia (PE). Effects of renal CD81 with sodium transporters were determined in lipopolysaccharide (LPS)-induced PE rats and immortalized mouse renal distal convoluted tubule cells. Urinary exosomal CD81, sodium potassium 2 chloride cotransporter (NKCC2), and sodium chloride cotransporter (NCC) were measured in PE patients. LPS-PE rats had hypertension from gestational days (GD) 6 to 18 and proteinuria from GD9 to GD18. Urinary CD81 in both groups tented to rise during pregnancy. Renal CD81, not sodium transporters, was higher in LPS-PE than controls on GD14. On GD18, LPS-PE rats exhibited higher CD81 in kidneys and urine exosomes, higher renal total and phosphorylated renal NKCC2 and NCC with elevated mRNAs, and lower ubiquitinated NCC than controls. CD81 was co-immunoprecipitated with NKCC2 or NCC in kidney homogenates and co-immunostained with NKCC2 or NCC in apical membranes of renal tubules. In plasma membrane fractions, LPS-PE rats had greater amounts of CD81, NKCC2, and NCC than controls with enhanced co-immunoprecipitations of CD81 with NKCC2 or NCC. In renal distal convoluted tubule cells, silencing CD81 with siRNA inhibited NCC and prevented LPS-induced NCC elevation. Further, PE patients had higher CD81 in original urines, urine exosomes and higher NKCC2 and NCC in urine exosomes than controls. Thus, the upregulation of renal CD81 on NKCC2 and NCC may contribute to the sustained hypertension observed in LPS-PE model. Urine CD81 with NKCC2 and NCC may be used as biomarkers for PE. CI - (c) 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology. FAU - Wang, Ping AU - Wang P AD - The Core Laboratory for Clinical Research, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China. AD - Department of Nephrology, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China. FAU - Zhu, Gangyi AU - Zhu G AD - The Core Laboratory for Clinical Research, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China. FAU - Wu, Qiaozhen AU - Wu Q AD - Department of Obstetrics and Gynecology, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China. FAU - Shen, Li AU - Shen L AD - Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. FAU - Liu, Dan AU - Liu D AD - Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. FAU - Wang, Zhiyin AU - Wang Z AD - Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. FAU - Wang, Weiwan AU - Wang W AD - The Core Laboratory for Clinical Research, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China. FAU - Ren, Zhiyun AU - Ren Z AD - The Core Laboratory for Clinical Research, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China. FAU - Jia, Yutao AU - Jia Y AD - Department of Nephrology, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China. FAU - Liu, Mingda AU - Liu M AD - The Core Laboratory for Clinical Research, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China. FAU - Xue, Ying AU - Xue Y AD - The Core Laboratory for Clinical Research, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China. FAU - Ji, Daxi AU - Ji D AD - Department of Nephrology, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China. FAU - Hu, Yali AU - Hu Y AD - Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. FAU - Yu, Yanting AU - Yu Y AUID- ORCID: 0000-0002-1631-2928 AD - The Core Laboratory for Clinical Research, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China. AD - Department of Nephrology, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China. FAU - Wang, Xiaoyan AU - Wang X AUID- ORCID: 0000-0001-7406-5008 AD - The Core Laboratory for Clinical Research, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China. AD - Department of Nephrology, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (Sodium-Potassium-Chloride Symporters) RN - 0 (Sodium Chloride Symporters) RN - 0 (Lipopolysaccharides) RN - 0 (Chlorides) RN - 0 (Solute Carrier Family 12, Member 1) RN - 9NEZ333N27 (Sodium) RN - RWP5GA015D (Potassium) RN - 0 (CD81 protein, human) RN - 0 (Tetraspanin 28) SB - IM MH - Pregnancy MH - Mice MH - Humans MH - Rats MH - Female MH - Animals MH - Sodium-Potassium-Chloride Symporters/metabolism MH - Sodium Chloride Symporters/genetics/metabolism MH - Lipopolysaccharides/toxicity/metabolism MH - Chlorides/metabolism MH - *Pre-Eclampsia/chemically induced/metabolism MH - Solute Carrier Family 12, Member 1/metabolism MH - Placenta/metabolism MH - Kidney Tubules, Distal/metabolism MH - *Hypertension/metabolism MH - Sodium/metabolism MH - Potassium/metabolism MH - Tetraspanin 28/metabolism OTO - NOTNLM OT - NCC OT - NKCC2 OT - mouse renal DCT cells OT - patients OT - rat preeclampsia model OT - renal CD81 EDAT- 2023/03/25 06:00 MHDA- 2023/03/28 17:16 CRDT- 2023/03/24 10:42 PHST- 2023/02/02 00:00 [revised] PHST- 2022/09/25 00:00 [received] PHST- 2023/02/10 00:00 [accepted] PHST- 2023/03/28 17:16 [medline] PHST- 2023/03/24 10:42 [entrez] PHST- 2023/03/25 06:00 [pubmed] AID - 10.1096/fj.202201546RR [doi] PST - ppublish SO - FASEB J. 2023 Apr;37(4):e22834. doi: 10.1096/fj.202201546RR.