61c7527417c6fe4e15eef3dfbc5e3f1c pmc_11545582.pdf 23de9942811f3a3bc569e9f7cc051b47df69bff5 pmc_11545582.pdf 2e170600154f8d607288094b6cffb674cfb371b38851179411ddede6b6a303e7 pmc_11545582.pdf Title: Neuropilin-1 as a Key Molecule for Renal Recovery in Lupus Nephritis: Insights from an NZB/W F1 Mouse Model Subject: Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organs, with lupus nephritis (LN) occurring in 40–50% of SLE patients. Despite advances in diagnosis and treatment, LN remains a major cause of morbidity and mortality, with 10–20% of patients progressing to end-stage renal disease (ESRD). While knowledge of LN’s pathogenesis has improved, mechanisms of renal recovery are still largely unexplored. Neuropilin-1 (NRP-1), a transmembrane receptor expressed in renal tissue, has emerged as a promising biomarker for assessing renal recovery in LN. This study evaluates and correlates longitudinal levels of NRP-1 with kidney histology using an NZB/W F1 mouse model of LN. A total of 30 mice were used, with 15 receiving intravenous cyclophosphamide (CYC) and 15 being untreated. NRP-1 levels were measured in urine and serum, and kidney samples were taken from a subgroup of mice for histological evaluation. The results demonstrated a progressive increase in renal and urinary NRP-1 expression, particularly notable at weeks 26 and 32. Urinary NRP-1 levels above 34.40 ng/mL were strong predictors of favorable renal response, showing 100% sensitivity and 88% specificity. These findings indicate a robust correlation between urinary NRP-1 levels and renal histological recovery, underscoring the potential of NRP-1 as a valuable biomarker for assessing renal response in LN. This study demonstrates that renal production of NRP-1 is linked to histological recovery and establishes a foundation for future research into the role of NRP-1 in lupus kidney recovery. Keywords: systemic lupus erythematosus (SLE); lupus nephritis (LN); neuropilin-1 (NRP-1); biomarker; renal recovery Author: Sebastian Sandoval, Cristina Solé, Blanca Joseph-Mullol, Maria Royo, Teresa Moliné, Alejandra Gabaldón and Josefina Cortés-Hernández Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Tue Oct 22 14:06:33 2024 CEST ModDate: Tue Oct 22 14:14:58 2024 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3246286 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ZZTQUO+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 OEOIAM+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 PGCLTX+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 VWPPJH+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 SXQPWE+VnURWPalladioL Type 1 Custom yes yes yes 32 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 48 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 51 0 OQIVQT+EURM10 Type 1 Builtin yes yes yes 71 0 IFEDSM+CMSY10 Type 1 Builtin yes yes yes 76 0 NGNPDO+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 90 0 NGNPDP+PalatinoLinotype CID TrueType Identity-H yes yes yes 93 0 NGNPEA+PalatinoLinotype TrueType WinAnsi yes yes no 99 0 NGNPEC+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 102 0 NGNPKC+PalatinoLinotype TrueType MacRoman yes yes no 105 0 NGNPDO+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 120 0 NGNPEA+PalatinoLinotype TrueType WinAnsi yes yes no 123 0 NGNPEC+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 126 0 NGNPKC+PalatinoLinotype TrueType MacRoman yes yes no 129 0 NGNPDO+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 144 0 NGNPDP+PalatinoLinotype CID TrueType Identity-H yes yes yes 147 0 NGNPEA+PalatinoLinotype TrueType WinAnsi yes yes no 153 0 NGNPEC+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 156 0 NGNPKC+PalatinoLinotype TrueType MacRoman yes yes no 159 0 PGDLOO+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 176 0 PGDLPP+PalatinoLinotype CID TrueType Identity-H yes yes yes 179 0 PGDMAA+PalatinoLinotype TrueType WinAnsi yes yes no 185 0 PGDMAC+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 188 0 PGDMGC+PalatinoLinotype TrueType MacRoman yes yes no 191 0 NGNPDO+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 205 0 NGNPDP+PalatinoLinotype CID TrueType Identity-H yes yes yes 208 0 NGNPEA+PalatinoLinotype TrueType WinAnsi yes yes no 214 0 NGNPEC+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 217 0 NGNPKC+PalatinoLinotype TrueType MacRoman yes yes no 220 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-02-06 02:46:22 CET RepresentationInformation: pmc_11545582.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-12-04 02:21:26 CET Size: 3246286 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 371 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Results Destination: section.2 Children: Item: Title: Cyclophosphamide Treatment Delays Disease Onset in NZB/W F1 Mice Destination: subsection.2.1 Item: Title: NRP-1 Expression Is Increased in the Kidneys of Treated NZB/W F1 Mice Destination: subsection.2.2 Item: Title: uNRP-1 Expression Inversely Correlates with Disease Biomarkers, Indicating a Role in Renal Recovery Destination: subsection.2.3 Item: Title: ROC Curve Analysis of uNRP-1 Levels for Predicting Renal Recovery in NZB/W F1 Mice Destination: subsection.2.4 Item: Title: Discussion Destination: section.3 Item: Title: Materials and Methods Destination: section.4 Children: Item: Title: Animal Models Destination: subsection.4.1 Item: Title: Histological Analysis of Renal Tissue Destination: subsection.4.2 Item: Title: Immunofluorescence for IgG, C3, or NRP-1 Protein Levels in Kidney Tissue Destination: subsection.4.3 Item: Title: Quantification of NRP-1 Levels in Blood and Urine Samples Destination: subsection.4.4 Item: Title: Determination of Anti-dsDNA and IgG Levels in Serum Destination: subsection.4.5 Item: Title: Determination of Urine Protein/Creatinine Ratio Destination: subsection.4.6 Item: Title: Statistical Analysis Destination: subsection.4.7 Item: Title: References Destination: appendix.A. Info: Title: Neuropilin-1 as a Key Molecule for Renal Recovery in Lupus Nephritis: Insights from an NZB/W F1 Mouse Model Author: Sebastian Sandoval, Cristina Solé, Blanca Joseph-Mullol, Maria Royo, Teresa Moliné, Alejandra Gabaldón and Josefina Cortés-Hernández Subject: Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organs, with lupus nephritis (LN) occurring in 40 50% of SLE patients. Despite advances in diagnosis and treatment, LN remains a major cause of morbidity and mortality, with 10 20% of patients progressing to end-stage renal disease (ESRD). While knowledge of LN’s pathogenesis has improved, mechanisms of renal recovery are still largely unexplored. Neuropilin-1 (NRP-1), a transmembrane receptor expressed in renal tissue, has emerged as a promising biomarker for assessing renal recovery in LN. This study evaluates and correlates longitudinal levels of NRP-1 with kidney histology using an NZB/W F1 mouse model of LN. A total of 30 mice were used, with 15 receiving intravenous cyclophosphamide (CYC) and 15 being untreated. NRP-1 levels were measured in urine and serum, and kidney samples were taken from a subgroup of mice for histological evaluation. The results demonstrated a progressive increase in renal and urinary NRP-1 expression, particularly notable at weeks 26 and 32. Urinary NRP-1 levels above 34.40 ng/mL were strong predictors of favorable renal response, showing 100% sensitivity and 88% specificity. These findings indicate a robust correlation between urinary NRP-1 levels and renal histological recovery, underscoring the potential of NRP-1 as a valuable biomarker for assessing renal response in LN. This study demonstrates that renal production of NRP-1 is linked to histological recovery and establishes a foundation for future research into the role of NRP-1 in lupus kidney recovery. 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