Journal: Journal of Translational Medicine

Article Title: Sodium-glucose cotransporter 2 inhibitors alleviate renal fibrosis in diabetic kidney disease by inhibiting Hmgcs2 and Btg2 in proximal tubular cells

doi: 10.1186/s12967-025-06788-6

Figure Lengend Snippet: SGLT2i downregulate the expression of Hmgcs2 in PT_S1 cells to prevent the fibrosis ( A ) PT_S1 cells were integrated into a single dataset and clustered using UMAP. Labels indicate different cell types. ( B ) Bar plot shows the Number of identified cell types in each sample. ( C ) Plotline plot shows the change of the proportion of Hmgcs2_PT_S1, Napsa PT_S1, Cela1 PT_S1and S100a8_PT_S1 in different groups. ( D ) Expression of selected marker genes for each cell type projected on UMAP. ( E-F ) The gene set variation analysis (GSVA) shows the EMT score and EMT expression on PT_S1 subclusters. ( G ) Bar plot shows the EMT expression in different groups. ( H ) Assessment of stemness in PT_S1. ( I ) Pseudo-Temporal analysis in PT_S1. ( J ) The Gene Regulatory Network (GRN) analysis showed that the Hmgcs2_PT_S1 was uniquely regulated by Egr1 in the M5 module. ( K ) scCor correlation analysis showed that Slc5a2 had a direct positive correlation with the expression of Hmgcs2.( p < 0.001) ( L ) KEGG enrichment analysis showed that the effect of SGLT2 on Hmgcs2_PT_S1 may be mediated through MAPK signaling pathways

Article Snippet: Immunofluorescent staining was conducted utilizing antibodies against Lrp2(bs-3909R, Bioss,1:200), Slc5a2, Hmgcs2 (bs-5070R, Bioss, 1:200), Btg2 (22339-1-AP, proteintech, 1:200) and Treble-Fluorescence immunohistochemical mouse/rabbit kit (RS0035, ImmunoWay) according to the manufacturer’s instructions.

Techniques: Expressing, Marker, Protein-Protein interactions

Journal: Journal of Translational Medicine

Article Title: Sodium-glucose cotransporter 2 inhibitors alleviate renal fibrosis in diabetic kidney disease by inhibiting Hmgcs2 and Btg2 in proximal tubular cells

doi: 10.1186/s12967-025-06788-6

Figure Lengend Snippet: SGLT2i decrease the number of Btg2_PT to suppress fibrotic changes in proximal tubular cells. ( A ) PT cells were integrated into a single dataset and clustered by UMAP. Labels indicate different cell types. ( B ) Bar plot shows the Number of identified cell types in each sample. (C) Plotline plot shows the change of the proportion of Btg2_PT, Gatm_PT, Col27a1_PT, Slco1a1_PT and Apoe_PT in different groups. ( D ) Expression of selected marker genes for each cell type projected on UMAP. ( E-F ) The gene set variation analysis (GSVA) shows the EMT score on PT subclusters. (CI 95% [-1.3%, -1.2%], p < 0.001). ( G ) Violin plot shows the EMT expression in different groups. ( H ) Assessment of stemness in PT. ( I ) Pseudo-Temporal analysis in PT. ( J ) Expression of top genes at different stages of differentiation ( K ) The Gene Regulatory Network (GRN) analysis showed that the Hmgcs2_PT_S1 was uniquely regulated by Egr1 in the M5 module. ( L ) KEGG enrichment analysis showed that the effect of SGLT2 on Btg2_PT may be mediated through MAPK signaling pathways * p < 0.05, ** p < 0.01, and *** p < 0.001

Article Snippet: Immunofluorescent staining was conducted utilizing antibodies against Lrp2(bs-3909R, Bioss,1:200), Slc5a2, Hmgcs2 (bs-5070R, Bioss, 1:200), Btg2 (22339-1-AP, proteintech, 1:200) and Treble-Fluorescence immunohistochemical mouse/rabbit kit (RS0035, ImmunoWay) according to the manufacturer’s instructions.

Techniques: Expressing, Marker, Protein-Protein interactions

Journal: Journal of Translational Medicine

Article Title: Sodium-glucose cotransporter 2 inhibitors alleviate renal fibrosis in diabetic kidney disease by inhibiting Hmgcs2 and Btg2 in proximal tubular cells

doi: 10.1186/s12967-025-06788-6

Figure Lengend Snippet: SGLT2i indirectly influences macrophages through cell-cell communication between proximal tubular cells and macrophages via the App-CD74 ligand-receptor pair ( A ) Cell communication analysis showed that interactions existed between epithelial cells and immune cells ( B-D ) the App-CD74 ligand-receptor pair exhibit higher activity and potential between Hmgcs2_PT_S1, Btg2_PT and Ctss_MAC. ( E ) The expression of App and CD74 in PT, PT_S1, macrophages and T lymphocytes clusters. ( F ) scCor correlation analysis showed that App had a direct positive correlation with fibrosis (CI 95% [2.33e-03, -0.02], p < 0.01)and the expression of Slc5a2 ( p < 0.001) in PT and PT_S1. ( G ) scCor correlation analysis showed that Cd74 had a direct negative correlation with inflammation (CI 95% [-0.41, -0.35], p < 0.001) and the expression of Slc5a2 ( p < 0.05)in Ctss_MAC

Article Snippet: Immunofluorescent staining was conducted utilizing antibodies against Lrp2(bs-3909R, Bioss,1:200), Slc5a2, Hmgcs2 (bs-5070R, Bioss, 1:200), Btg2 (22339-1-AP, proteintech, 1:200) and Treble-Fluorescence immunohistochemical mouse/rabbit kit (RS0035, ImmunoWay) according to the manufacturer’s instructions.

Techniques: Activity Assay, Expressing

Journal: Journal of Translational Medicine

Article Title: Sodium-glucose cotransporter 2 inhibitors alleviate renal fibrosis in diabetic kidney disease by inhibiting Hmgcs2 and Btg2 in proximal tubular cells

doi: 10.1186/s12967-025-06788-6

Figure Lengend Snippet: Validation of Hmgcs2 and Btg2 on mice ( A ) Glucose of mice from different groups. ( B ) Weight of mice from different groups. ( C ) UPCR of mice from different groups. (CI 95% [14.29, 74.07], p < 0.05) ( D ) Representative immunofluorescence images from each group for LRP2(PT marker, red) and SGLT2 (PT-S1 marker, green), and BTG2/HMGCS2 (yellow) ( E ) Representative HE and immunohistochemistry of α-SMA images from each group. * p < 0.05, ** p < 0.01, and *** p < 0.001

Article Snippet: Immunofluorescent staining was conducted utilizing antibodies against Lrp2(bs-3909R, Bioss,1:200), Slc5a2, Hmgcs2 (bs-5070R, Bioss, 1:200), Btg2 (22339-1-AP, proteintech, 1:200) and Treble-Fluorescence immunohistochemical mouse/rabbit kit (RS0035, ImmunoWay) according to the manufacturer’s instructions.

Techniques: Biomarker Discovery, Immunofluorescence, Marker, Immunohistochemistry

Journal: Journal of Translational Medicine

Article Title: Sodium-glucose cotransporter 2 inhibitors alleviate renal fibrosis in diabetic kidney disease by inhibiting Hmgcs2 and Btg2 in proximal tubular cells

doi: 10.1186/s12967-025-06788-6

Figure Lengend Snippet: Validation of HMGCS2 and BTG2 on human ( A ) Representative immunofluorescence images from human renal slices for LRP2(PT marker, red) and SGLT2 (PT-S1 marker, green), and BTG2/HMGCS2 (yellow) ( B ) Representative western blot images from each group for Hmgcs2, Btg2 and Gapdh in hRPTC. ( C ) Representative western blot images from each group for Hmgcs2, Btg2 and Gapdh in HK-2 cells. ( D ) The RT-qPCR results showed that down-regulation of SLC5A2(CI 95% [-1.03, -0.87]) in HK-2 cells could directly up-regulate the RNA expression levels of HMGCS2 (CI 95% [2.75, 7.55]) and BTG2(CI 95% [1.06, 3.19]). n = 3/group. Means (± S.E.) of n = 3 independent experiments. * p < 0.05, ** p < 0.01, and *** p < 0.001

Article Snippet: Immunofluorescent staining was conducted utilizing antibodies against Lrp2(bs-3909R, Bioss,1:200), Slc5a2, Hmgcs2 (bs-5070R, Bioss, 1:200), Btg2 (22339-1-AP, proteintech, 1:200) and Treble-Fluorescence immunohistochemical mouse/rabbit kit (RS0035, ImmunoWay) according to the manufacturer’s instructions.

Techniques: Biomarker Discovery, Immunofluorescence, Marker, Western Blot, Quantitative RT-PCR, RNA Expression