Background Evidence has accumulated that hypoxia played a significant role in the pathogenesis and progression of both acute renal injury and chronic renal disease.
Objectives In this study, the expression of hypoxia inducible factor-1 alpha (HIF-1α) in lupus nephritis (LN) was explored.
Methods Renal biopsy samples from 23 LN patients and 20 patients with renal carcinoma were obtained. The expression of HIF-1α was examined using immunohistochemical staining, and their correlations with clinical and pathological features were assessed. To confirm the results in human study, HIF-1α expression in kidney sections from both MRL/lpr and C57BL/6J mice was measured. Dimethyloxaloylglycine (DMOG), inhibitor of HIF-degrading prolylhydroxylases, was applied to detect the effect of HIF-1α on cell proliferation in mouse glomerular mesangial cell line by CCK8 assay.
Results Tissues from LN patients exhibited higher HIF-1α expression in both glomerular (81.50±1.55% vs 60.52±5.00%, p<0.001) and tubulointerstitial location (80.25±1.94% vs 65.40±4.19%, p<0.01) than the tumor surrounding tissues from patients with renal carcinoma. HIF-1α was significantly elevated in class IV LN compared to other pathological types. There were associations between intraglomerular number of HIF-1α-positive cells and renal pathology activity index as well as several clinical variables in LN patients, including Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), urinary protein and serum albumin. Intraglomerular HIF-1α-positive cells in MRL/lpr mice were also significantly increased (70.88±4.91% vs 34.50±5.94%, p<0.001). After DMOG stimulation, the proliferation rate of glomerular mesangial cells was significantly elevated (OD value 1.32±0.03 vs. 1.11±0.0, p<0.001).
Conclusions HIF-1α is highly expressed in both glomerular and tubulointerstitial tissues in LN, especially in class IV LN. High expression of HIF-1α can promote the proliferation of glomerular mesangial cells, thus may represent a novel target for LN therapy.
Disclosure of Interest None declared
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