Beraprost sodium mitigates renal interstitial fibrosis through repairing renal microvessels
- 253 Downloads
Beraprost sodium (BPS), as a prostacyclin analog, plays a significant role in various diseases based on its antiplatelet and vasodilation functions. However, its regulation and role in chronic kidney disease (CKD) still remain elusive. Here, we determined whether BPS could alleviate renal interstitial fibrosis, and improve the renal function and its therapeutic mechanism. In vitro, BPS increased angiogenesis in the HUVECs incubated with BPS detected by tube formation assay and repair damaged endothelial cell–cell junctions induced by hypoxia. In vivo, mice were randomly assigned to a sham-operation group (sham), a unilateral ureteral obstruction group (UUO), and a BPS intragastrical administration group (BPS), and sacrificed at days 3 and 7 post-surgery (six in each group). In UUO model, tissue hypoxia, renal inflammation, oxidative stress, and fibrotic lesions were detected by q-PCR and Western blot techniques and peritubular capillaries (PTCs) injury was detected by a novel technique of fluorescent microangiography (FMA) and analyzed by MATLAB software. Meanwhile, we identified cells undergoing endothelial cell-to-myofibroblast transition by the coexpression of endothelial cell (CD31) and myofibroblast (a-SMA) markers in the obstructed kidney. In contrast, BPS protected against interstitial fibrosis and substantially reduced the number of endothelial cell-to-myofibroblast transition cells. In conclusion, our data indicate the potent therapeutic of BPS in mitigating fibrosis through repairing renal microvessels and suppressing endothelial-mesenchymal transition (EndMT) progression after inhibiting inflammatory and oxidative stress effects.
BPS could improve renal recovery through anti-inflammatory and anti-oxidative pathways.
BPS could mitigate fibrosis through repairing renal microvessels and suppressing endothelial-mesenchymal transition (EndMT).
KeywordsBeraprost sodium Peritubular capillaries Inflammation Oxidative stress Endothelial-mesenchymal transition Renal interstitial fibrosis
This study was supported by funding from the National Natural Science Foundation of China (81270769); the Jiangsu Provincial Natural Science Foundation (BK20161172); the Jiangsu Provincial Commission of Health and Family Planning (2016103003); a project of the Jiangsu Provincial Commission of Health and Family Planning (H201628); a project of Qing Lan of Jiangsu Province; a project of “Liu Ge Yi” of Jiangsu Province (LGY2016043); the project of “Liu Da Ren Cai Gao Feng” of Jiangsu Province, China (WSN-113, 2010-WS043); the Technology Development Foundation of Kuitun City (201134); the Jiangsu Overseas Training Program for University Prominent Young and Middle-aged Teachers and Presidents; and Shi Er Wu Ke Jiao Xing Wei Key Medical Personnel of Jiangsu Province (RC2011116); a school class project of Xuzhou Medical University (2017KJ13); Municipal key research and development project of Xuzhou (KC18212); a project of Jiangsu Provincial Post Graduate Innovation Plan (KYCX17_1708, SJCX17_0560, KYCX18-2178, SJCX18_0715).
Compliance with ethical standards
- 7.Li S, Zhao Y, Wang Z, Wang J, Liu C, Sun D (2018) Transplantation of amniotic fluid-derived stem cells preconditioned with glial cell line-derived neurotrophic factor gene alleviates renal fibrosis. Cell Transplant 28:963689718815850Google Scholar
- 9.Eardley KS, Kubal C, Zehnder D, Quinkler M, Lepenies J, Savage CO, Howie AJ, Kaur K, Cooper MS, Adu D, Cockwell P (2008) The role of capillary density, macrophage infiltration and interstitial scarring in the pathogenesis of human chronic kidney disease. Kidney Int 74(4):495–504CrossRefGoogle Scholar
- 15.Matsumoto T, Iwasa K, Kyuragi R, Honma K, Guntani A, Ohmine T, Itoh H, Onohara T, Maehara Y (2010) The efficacy of oral beraprost sodium, a prostaglandin I2 analogue, for treating intermittent claudication in patients with arteriosclerosis obliterans. Int Angiol 29(2 Suppl):49–54Google Scholar
- 20.Zhang L, Wang F, Wang L, Wang W, Liu B, Liu J, Chen M, He Q, Liao Y, Yu X, Chen N, Zhang JE, Hu Z, Liu F, Hong D, Ma L, Liu H, Zhou X, Chen J, Pan L, Chen W, Wang W, Li X, Wang H (2012) Prevalence of chronic kidney disease in China: a cross-sectional survey. Lancet 379(9818):815–822CrossRefGoogle Scholar