Abstract | BACKGROUND: METHODS: Thirty-four MRL/lpr mice were randomly divided into the following three groups: MRL/lpr, saline, and anti- P-selectin, which consisted of no treatment, treatment with normal saline, and treatment with anti- P-selectin monoclonal antibody (mAb) from 12 to 16 weeks of age, respectively. Ten male C57BL/6 mice of the same age served as normal controls. 24-h urinary protein, urinary albumin- creatinine ratio, and periodic acid-Schiff were used to assess kidney damage; Western blot or immunohistochemical staining of the hypoxia probe Hypoxyprobe™-1, hypoxia-inducible factor 1α (HIF-1α), and CD31 were used to evaluate hypoxia in renal tissue; and NADPH oxidase subunit gp91phox and p22phox were used to examine renal oxidative stress. The correlation between kidney injury and blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) was calculated to assess the clinical value of BOLD-MRI. RESULTS:
P-selectin is upregulated in lupus nephritis. Blocking P-selectin with mAb alleviated renal tubulointerstitial fibrosis, renal hypoxia, and peritubular capillary loss, without alteration of the levels of lupus activity indicators, anti-dsDNA antibody, or complement C3. BOLD-MRI showed that the reduced R2* values in the renal cortex and medulla of lupus mice were increased when treated with anti- P-selectin mAb as compared with those treated with normal saline, which were negatively correlated with Hypoxyprobe™-1 hypoxia probe and the expression of HIF-1α. CONCLUSIONS: Early intervention of lupus nephritis with anti- P-selectin mAb can significantly improve the hypoxic state of the kidney and reduce the severity of tubulointerstitial lesions. BOLD-MRI techniques are noninvasive and can dynamically evaluate the changes in renal lesions and intrarenal oxygenation levels before and after treatment in lupus nephritis.
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Authors | Liwen Zhang, Sheng Chen, Yan Liu, Xueqin Xu, Qianying Zhang, Shuxin Shao, Weiming Wang, Xiao Li |
Journal | Journal of translational medicine
(J Transl Med)
Vol. 18
Issue 1
Pg. 116
(03 05 2020)
ISSN: 1479-5876 [Electronic] England |
PMID | 32138730
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Animals
- Hypoxia
- Ischemia
- Kidney
- Lupus Nephritis
(drug therapy)
- Magnetic Resonance Imaging
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Inbred MRL lpr
- P-Selectin
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