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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)\u2010induced 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\u2010PE 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\u2010PE than controls on GD14. On GD18, LPS\u2010PE 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\u2010immunoprecipitated with NKCC2 or NCC in kidney homogenates and co\u2010immunostained with NKCC2 or NCC in apical membranes of renal tubules. In plasma membrane fractions, LPS\u2010PE rats had greater amounts of CD81, NKCC2, and NCC than controls with enhanced co\u2010immunoprecipitations of CD81 with NKCC2 or NCC. In renal distal convoluted tubule cells, silencing CD81 with siRNA inhibited NCC and prevented LPS\u2010induced 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\u2010PE model. Urine CD81 with NKCC2 and NCC may be used as biomarkers for PE.<\/jats:p>","DOI":"10.1096\/fj.202201546rr","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T10:35:23Z","timestamp":1679654123000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Renal CD81 interacts with sodium potassium 2 chloride cotransporter and sodium chloride cotransporter in rats with lipopolysaccharide\u2010induced preeclampsia"],"prefix":"10.1096","volume":"37","author":[{"given":"Ping","family":"Wang","sequence":"first","affiliation":[{"name":"The Core Laboratory for Clinical Research, BenQ Medical Center The Affiliated BenQ Hospital of Nanjing Medical University  Nanjing China"},{"name":"Department of Nephrology, BenQ Medical Center The Affiliated BenQ Hospital of Nanjing Medical University  Nanjing 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