High-Salt Diet Aggravates Endothelial-to-Mesenchymal Transition in Glomerular Fibrosis in Dahl Salt-Sensitive Rats

Abstract

Background: Both diabetic and hypertensive nephropathy eventually progress to glomerulosclerosis. Previous studies revealed a potential role of endothelial-to-mesenchymal transition (EndMT) in the pathophysiology of glomerulosclerosis in diabetic rats. Therefore, we hypothesized that EndMT was also involved in the development of glomerulosclerosis in salt-sensitive hypertension. We aimed to explore the effects of high-salt diet on endothelial-to-mesenchymal transition (EndMT) in glomerulosclerosis in Dahl salt-sensitive (Dahl-SS) rats.

Methods: Eight-week-old male rats were fed high-salt (8%NaCl; DSH group) or normal salt (0.3%NaCl; DSN group) for eight weeks, with systolic blood pressure (SBP), serum creatinine, urea, 24-hour urinary protein/sodium, renal interlobar artery blood flow, and pathological examination measured. We also examined endothelial-(CD31) and fibrosis-related protein(α-SMA) expressions in glomeruli.

Results: High-salt diet increased SBP (DSH vs. DSN, 205.2 ± 8.9 vs. 135.4 ± 7.9 mm Hg, P < 0.01), 24-hour urinary protein (132.55 ± 11.75 vs. 23.52 ± 5.94 mg/day, P < 0.05), urine sodium excretions (14.09 ± 1.49 vs. 0.47 ± 0.06 mmol/day, P < 0.05), and renal interlobar artery resistance. Glomerulosclerosis increased (26.1 ± 4.6 vs. 7.3 ± 1.6%, P < 0.05), glomerular CD31 expressions decreased while α-SMA expression increased in DSH group. Immunofluorescence staining showed that CD31 and α-SMA co-expressed in glomeruli of the DSH group. The degree of glomerulosclerosis negatively correlated with CD31 expressions (r = -0.823, P < 0.01) but positively correlated with α-SMA expressions (r = 0.936, P < 0.01).

Conclusions: We demonstrated that a high-salt diet led to glomerulosclerosis involving the EndMT process, which played an essential role in glomerulosclerosis in hypertensive Dahl-SS rats.

Keywords: blood pressure; endothelial; glomerulosclerosis; hypertension; hypertensive nephropathy; mesenchymal transformation (EndMT); salt; sensitive hypertension (SSHT); to.