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Journal: Nature Communications
Article Title: Renal insulin-like growth factor binding-protein 7 is a critical promoter of progressive diabetic kidney disease
doi: 10.1038/s41467-025-66490-5
Figure Lengend Snippet: A Schematic diagram showing induction of type 1 diabetic kidney disease in IGFBP7 renal tubular epithelial cell conditional knockout (cKO) mice. Art was created by FigDraw 2.0. B Urinary albumin/creatinine level of FF and cKO mice. The results showed that knockout IGFBP7 in tubular significantly reduced STZ-induced glomerular dysfunction ( n = 8 biological replicates, one-way ANOVA with Tukey’s multiple comparisons test). C PAS and Masson staining of renal tubules. Scale bars, 20 and 50 μm. D Schematic diagram showing induction of type 2 diabetic kidney disease in cKO mice. Art was created by FigDraw 2.0. E Oil red O and immunofluorescence staining of kidney tissues from HFD/STZ-treated FF and cKO mice. F Urinary albumin/creatinine level of FF and cKO mice. The results showed that cKO mice significantly reduced HFD/STZ induced type 2 diabetic kidney disease ( n = 6 biological replicates, one-way ANOVA with Tukey’s multiple comparisons test). G PCA plot of the kidney lipidomics analysis of FF + HFD/STZ and cKO+HFD/STZ mice ( n = 5). H Heat map showing DEGs related to Phosphatidylcholine (PC) in FF and cKO mouse kidney ( n = 5). I In vivo imaging analysis of IGFBP7 cKO mice. IGFBP7 expression in the kidneys was successfully restored by tubule-targeted AAV in cKO mice. J Immunofluorescence results of KIM-1 and αSMA in IGFBP7 cKO mice. K Schematic diagram showing induction of type 2 diabetic kidney disease in IGFBP7 renal podocyte conditional knockout (cKO Nphs1 ) mice. Art was created by FigDraw 2.0. L Transmission electron microscopy of glomerular basement membrane thickness and foot process width in FF and cKO Nphs1 mice. Data represent the mean ± SEM. FF floxflox, cKO conditional knockout in tubular, cKO Nphs1 conditional knockout in podocyte, PC phosphatidylcholine, LPC lyso phosphatidylcholin, EV empty vector, OE overexpression. Source data are provided as a Source Data file.
Article Snippet: Antibodies specific for IGFBP7 (ab171085, ab214262: Abcam; and 19961-1-AP: Proteintech), COL-1 (66761-1-Ig; Proteintech),
Techniques: Knock-Out, Staining, Immunofluorescence, In Vivo Imaging, Expressing, Transmission Assay, Electron Microscopy, Membrane, Plasmid Preparation, Over Expression
Journal: Nature Communications
Article Title: Renal insulin-like growth factor binding-protein 7 is a critical promoter of progressive diabetic kidney disease
doi: 10.1038/s41467-025-66490-5
Figure Lengend Snippet: A KEGG enrichment analysis of upregulated (above) and downregulated (down) genes following IGFBP7 overexpression (P adj. Value, false discovery rate). B GSEA plots of fatty acid metabolism gene sets. C KEGG module analysis of fatty acid metabolism. The results showed a significant enrichment in the fatty acid β-oxidation pathway (P adj. Value, false discovery rate). D GSEA plots for oxidative phosphorylation and TCA cycle genes. E Real-time PCR analysis of the mRNA expression of electron transport chain (ETC, Complex I–V) complex genes in BP7-Tg and WT kidney at 8 months of age ( n = 6, two-tailed unpaired Student’s t test). F Western blot of PGC-1α in FF versus cKO mice ( n = 6, one-way ANOVA with Tukey’s multiple comparisons test). G Real-time monitoring the oxygen consumption rate (OCR) in HK2 with or without IGFBP7 overexpression (BP7-EV ( n = 3), BP7-OE ( n = 4); biological replicates). H Real-time monitoring the OCR in HG-treated HK2 with or without IGFBP7 knockdown ( n = 3). I Relative OCR of HG-treated HK2 with or without IGFBP7 overexpression ( n = 12, two-tailed unpaired Student’s t test). J Etomoxir-induced decreases in OCR from HG-treated HK2 ( n = 12, two-tailed unpaired Student’s t test). K Schematic of the mechanism by which IGFBP7 induces impaired fatty acid degradation and lipid accumulation in renal tubular epithelial cells; key components and inhibitors involved are shown (by FigDraw 2.0). L Schematic of in vitro co-culture experiments. M Western blot analysis of Wilms’ Tumer 1 (WT-1) and Nephrin protein levels in MPC5 cells under mTEC conditioned media ( n = 4, one-way ANOVA with Tukey’s multiple comparisons test). N Western blot analysis of COL-1 and αSMA protein levels in NIH-3T3 cells under mTEC conditioned media ( n = 4, one-way ANOVA with Tukey’s multiple comparisons test). O Kidney spheroids from FF and IGFBP7-cKO mice. P Western blotting and quantification of COL-1 and αSMA in FF and cKO mouse kidney spheroids treated with high glucose ( n = 3, one-way ANOVA with Tukey’s multiple comparisons test). Data represent the mean ± SEM. n.s. not significant, FF floxflox, cKO conditional knockout in tubular, WT wild type, BP7-Tg IGFBP7 overexpression transgenic, HG high glucose, EV empty vector, OE overexpression. Source data are provided as a Source Data file.
Article Snippet: Antibodies specific for IGFBP7 (ab171085, ab214262: Abcam; and 19961-1-AP: Proteintech), COL-1 (66761-1-Ig; Proteintech),
Techniques: Over Expression, Phospho-proteomics, Real-time Polymerase Chain Reaction, Expressing, Two Tailed Test, Western Blot, Knockdown, In Vitro, Co-Culture Assay, Knock-Out, Transgenic Assay, Plasmid Preparation
Journal: Nature Communications
Article Title: Renal insulin-like growth factor binding-protein 7 is a critical promoter of progressive diabetic kidney disease
doi: 10.1038/s41467-025-66490-5
Figure Lengend Snippet: A Schematic diagram showing induction of type 1 diabetic kidney disease in STAT3 renal tubular epithelial cell conditional knockout (S3cKO) mice. Art was created by FigDraw 2.0. B Urinary albumin/creatinine level of S3FF and S3cKO mice. The results showed that knockout STAT3 in tubular significantly reduced STZ-induced glomerular dysfunction ( n = 6 biological replicates, one-way ANOVA with Tukey’s multiple comparisons test). C Masson and immunohistochemical staining results of STZ-treated S3cKO mice. Scale bars, 50 μm. D Schematic illustration of overexpression of STAT3 in IGFBP7 renal tubule conditional knockout (cKO) mice. E Immunofluorescence results of mouse kidney STAT3 expression levels. The results showed that STAT3 was successfully overexpressed in cKO mice. F PAS, Masson, and immunohistochemistry staining in cKO mice with STAT3 overexpression. Scale bars, 50 μm. G Urinary albumin/creatinine level in STZ-treated IGFBP7 cKO mice with STAT3 overexpression ( n = 6 biological replicates, one-way ANOVA with Tukey’s multiple comparisons test). H Western blot analysis of NLRP3, COL-1, αSMA, KIM-1, and STAT3. I PAS and Masson staining of IGFBP7 cKO mice kidney. Scale bars, 50 μm. J Urinary albumin/creatinine level in HFD/STZ-treated IGFBP7 cKO mice with STAT3 overexpression ( n = 6 biological replicates, one-way ANOVA with Tukey’s multiple comparisons test). K Schematic representation of STAT3 silencing in IGFBP7 overexpression transgenic (Tg) mice. L PAS and Masson staining of IGFBP7 Tg mice kidney ( n = 6 biological replicates, two-tailed unpaired Student’s t test). Scale bars, 50 μm. M Urinary albumin/creatinine level in STZ-treated IGFBP7 Tg mice with STAT3 knockdown ( n = 6 biological replicates, two-tailed unpaired Student’s t test). Data represent the mean ± SEM. Source data are provided as a Source Data file.
Article Snippet: Antibodies specific for IGFBP7 (ab171085, ab214262: Abcam; and 19961-1-AP: Proteintech), COL-1 (66761-1-Ig; Proteintech),
Techniques: Knock-Out, Immunohistochemical staining, Staining, Over Expression, Immunofluorescence, Expressing, Immunohistochemistry, Western Blot, Transgenic Assay, Two Tailed Test, Knockdown
Journal: Nature Communications
Article Title: Renal insulin-like growth factor binding-protein 7 is a critical promoter of progressive diabetic kidney disease
doi: 10.1038/s41467-025-66490-5
Figure Lengend Snippet: A Workflow of the hybrid virtual screening strategy. B Molecular docking demonstrated that Levomefolic acid (LA) physically bound to the catalytic domain of IGFBP7. C Cellular thermal shift assay (CETSA) analysis showing the stabilisation of IGFBP7 in vitro, with or without LA treatment. D Surface plasmon resonance (SPR) analysis of the interactions between IGFBP7 and LA. Concentration of salmeterol (μmol/L): 16, 8, 4, 2, 1, 0.5. E Immunofluorescence (IF) analysis of COL-1 and αSMA in LA-treated HK2 cells in response to high glucose (HG). F Schematic illustration of treatment of levomefolic acid after STZ-induced type 1 diabetic kidney disease. G Urinary albumin/creatinine level in STZ-induced DKD with LA treatment ( n = 6 biological replicates, one-way ANOVA with Tukey’s multiple comparisons test). H PAS and Masson staining in STZ-induced DKD with LA treatment. Scale bars, 50 μm. I Oil red O staining of STZ-induced DKD with LA treatment. Scale bars, 100 μm. J Schematic illustration of treatment of LA after HFD/STZ-induced type 2 diabetic kidney disease. K Urinary albumin/creatinine level in HFD/STZ-induced DKD with LA treatment ( n = 6 biological replicates, one-way ANOVA with Tukey’s multiple comparisons test). L PAS and Masson staining in HFD/STZ-induced DKD with LA treatment ( n = 6 biological replicates, one-way ANOVA with Tukey’s multiple comparisons test). Scale bars, 50 μm. Data represent the mean ± SEM. Source data are provided as a Source Data file.
Article Snippet: Antibodies specific for IGFBP7 (ab171085, ab214262: Abcam; and 19961-1-AP: Proteintech), COL-1 (66761-1-Ig; Proteintech),
Techniques: Thermal Shift Assay, In Vitro, SPR Assay, Concentration Assay, Immunofluorescence, Staining