SGLT-2 expression increases with glucose concentration and duration of high-glucose peritoneal dialysis solution, exacerbating peritoneal fibrosis, inflammation, and vascular lesions

@article{qingli2026sglt2,
  title = {{SGLT-2 expression increases with glucose concentration and duration of high-glucose peritoneal dialysis solution, exacerbating peritoneal fibrosis, inflammation, and vascular lesions}},
  author = {Cai Qingli and Cai Mingyu},
  journal = {陆军军医大学学报},
  year = {2026},
  month = oct,
  doi = {10.16016/j.2097-0927.202607051},
  url = {https://doi.org/10.16016/j.2097-0927.202607051},
  note = {CC BY},
}

TY  - JOUR
TI  - SGLT-2 expression increases with glucose concentration and duration of high-glucose peritoneal dialysis solution, exacerbating peritoneal fibrosis, inflammation, and vascular lesions
AU  - Cai Qingli
AU  - Cai Mingyu
PY  - 2026
DA  - 2026/10/30
JO  - 陆军军医大学学报
DO  - 10.16016/j.2097-0927.202607051
UR  - https://doi.org/10.16016/j.2097-0927.202607051
AB  - Objective Peritoneal dialysis (PD) is an important renal replacement therapy for end-stage renal disease, but long-term exposure to high-glucose dialysate can induce peritoneal fibrosis, inflammation, and vascular lesions, leading to ultrafiltration failure. Sodium‑glucose cotransporter 2 (SGLT‑2) is expressed in peritoneal tissues and may participate in high glucose‑induced peritoneal injury. This study aimed to investigate the expression, localization, and dynamic changes of SGLT-2 in peritoneal tissues from PD patients and a mouse model of high-glucose peritoneal dialysis solution, and to analyze the quantitative relationship between SGLT-2 expression and peritoneal pathological injury, thereby providing experimental evidence for SGLT-2 as a potential biomarker of peritoneal injury and for a subsequent intervention target. Methods ① Twenty-five patients with end-stage renal disease who underwent peritoneal dialysis catheterization for the first time in Department of Nephrology of our hospital between December 2024 and December 2025 were enrolled. Immunohistochemistry (IHC) and immunofluorescence double staining were used to detect the expression and localization of SGLT-2 in peritoneal tissues of PD patients. ② Sixty SPF male C57BL/6 mice [6 to 8 weeks old, weighing (22.5±1.5) g] were subjected to establish a peritoneal injury model induced by 7.00% glucose peritoneal dialysis solution. Peritoneal tissues from mice after 1 week of induction were collected, and IHC and immunofluorescence double staining were employed to detect the expression and localization of SGLT-2. Peritoneal tissues were harvested at weeks 1, 4, 8, and 12, respectively; HE staining was performed to evaluate peritoneal pathological injury, and IHC was applied to observe time-dependent changes in SGLT-2 expression. Mouse models treated with 2.50%, 4.25%, and 7.00% glucose peritoneal dialysis solutions were constructed. After 12 weeks of intervention, peritoneal tissue samples were collected; HE staining and IHC were carried out to observe peritoneal pathological injury and concentration-dependent changes in SGLT-2 expression. Spearman correlation analysis was utilized to analyze the correlation between SGLT-2 expression and the degree of peritoneal histopathological injury (submesothelial layer thickness, acute and chronic inflammation scores, and vascular lesion score). ③ Human peritoneal mesothelial cells (HPMCs) and human umbilical vein endothelial cells (HUVECs) stimulated with 30 mmol/L high glucose were established, and RT-qPCR was used to detect the mRNA expression of SGLT-2. Results ① SGLT-2 was mainly expressed in peritoneal mesothelial cells and vascular endothelial cells in peritoneal tissues of PD patients.② SGLT-2 was mainly expressed in peritoneal mesothelial cells and vascular endothelial cells in peritoneal tissues of PD mice. Induction with 7.00% high-glucose peritoneal dialysis solution significantly upregulated SGLT-2 expression in mouse peritoneal tissues, which gradually increased with the prolongation of induction time and reached a peak at 12 weeks. Compared with the control group, the percentage of SGLT-2-positive cells was significantly increased in the 8- and 12-week groups (P<0.000 1), and was higher in the 12-week group than in the 8-week group (P=0.013 3). With the increase of glucose concentration in peritoneal dialysis solution, the expression level of SGLT-2 in mouse peritoneal tissue was gradually upregulated. At 12 weeks, SGLT-2 expression in the peritoneal tissue of mice treated with 7.00% high-glucose peritoneal dialysate was significantly higher than that in mice treated with 4.25% high-glucose peritoneal dialysate (P<0.000 1). HE staining showed that the thickness of the submesothelial layer, inflammation, and fibrosis of the peritoneum aggravated with the increase of concentration. Correlation analysis revealed that the expression level of SGLT-2 was significantly positively correlated with submesothelial layer thickness (r=0.766 5, P<0.000 1), chronic inflammation score (r=0.921 0, P<0.000 1), and vascular lesion score (r=0.882 9, P<0.000 1), but not significantly correlated with acute inflammation score (r=0.223 9, P=0.297 3). ③ In vitro experiments demonstrated that high-glucose stimulation significantly upregulated the mRNA and protein expression of SGLT-2 in HPMCs and HUVECs, with peak expression at 24 h. Conclusion High-glucose microenvironment upregulates the expression of peritoneal SGLT-2, and its level is closely associated with peritoneal inflammation, fibrosis, and vascular lesions. SGLT-2 may be involved in the process of high-glucose-induced peritoneal injury and is expected to serve as a potential biomarker for peritoneal injury assessment and as a therapeutic target.
SN  - 2097-0927
ER  -