Cardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, UMR 1116 Université de Lorraine, CHRU de Nancy, French-Clinical Research Infrastructure Network (F-CRIN) INI-CRCT, Nancy, France.
J Hypertens. 2018 Feb;36(2):368-376. doi: 10.1097/HJH.0000000000001545.
The pharmacological blockade of galectin-3 (Gal-3), a β-galactoside-binding lectin, reduces renal impairment in acute kidney injury, hyperaldosteronism or nephropathy. We herein investigated the effects of pharmacological Gal-3 inhibition by modified citrus pectin (MCP) in renal damage in spontaneously hypertensive rats (SHRs).
Gal-3 inhibition did not modify blood pressure levels in 30-week-old SHR. Kidney weight was higher in SHR, with no effect of MCP treatment (100 mg/kg/day in the drinking water). Plasma creatinine and albuminuria were slightly but significantly increased in SHR and reduced by MCP, as well as plasma and urinary neutrophil gelatinase-associated lipocalin. In kidney from SHR, Gal-3 was upregulated, as well as the fibrotic markers (collagen type I, TGF-β and connective tissue growth factor) and tubulointerstitial fibrosis. MCP treatment reduced Gal-3 levels and fibrosis. The epithelial-mesenchymal transition (EMT) molecules (fibronectin, α-smooth muscle actin and β-catenin) were modified in SHR and normalized by Gal-3 inhibition. The inflammatory mediators (monocyte chemoattractant protein-1, osteopontin, cd68, cd80, cd44 and cd45) were elevated in SHR and attenuated by MCP. Renal damage markers (neutrophil gelatinase-associated lipocalin and kidney injury molecule-1) were augmented in SHR and improved by MCP. In renal epithelial normal rat kidney-52E cells, Gal-3 treatment induced EMT markers, whereas Gal-3 silencing attenuated EMT.
Gal-3 inhibition attenuated early renal damage in SHR as indicated by reduced albuminuria, improved renal function and decreased renal fibrosis, EMT and inflammation, independently of blood pressure levels. These data suggest that Gal-3 could be a potential therapeutic candidate for the prevention of early renal alterations in hypertension.
半乳糖凝集素-3（Gal-3）是一种β-半乳糖苷结合凝集素，其药理学阻断可减轻急性肾损伤、醛固酮增多症或肾病中的肾功能损害。在此，我们研究了改良柑橘果胶（MCP）对自发性高血压大鼠（SHR）肾损伤中Gal-3 抑制的作用。
Gal-3 抑制在 30 周龄 SHR 中并未改变血压水平。SHR 的肾脏重量更高，但 MCP 处理无影响（饮用水中 100mg/kg/天）。SHR 的血浆肌酐和白蛋白尿略有但显著升高，并被 MCP 降低，以及血浆和尿中性粒细胞明胶酶相关脂质运载蛋白。在 SHR 的肾脏中，Gal-3 上调，以及纤维化标志物（I 型胶原、TGF-β和结缔组织生长因子）和肾小管间质纤维化。MCP 治疗降低了 Gal-3 水平和纤维化。上皮-间充质转化（EMT）分子（纤连蛋白、α-平滑肌肌动蛋白和β-连环蛋白）在 SHR 中被改变，并被 Gal-3 抑制正常化。炎症介质（单核细胞趋化蛋白-1、骨桥蛋白、cd68、cd80、cd44 和 cd45）在 SHR 中升高，并被 MCP 减弱。SHR 中肾脏损伤标志物（中性粒细胞明胶酶相关脂质运载蛋白和肾损伤分子-1）增加，并被 MCP 改善。在正常大鼠肾上皮细胞-52E 细胞中，Gal-3 处理诱导 EMT 标志物，而 Gal-3 沉默则减弱 EMT。
Gal-3 抑制减轻了 SHR 的早期肾损伤，表现为白蛋白尿减少、肾功能改善和肾纤维化、EMT 和炎症减少，与血压水平无关。这些数据表明，Gal-3 可能是预防高血压早期肾脏改变的潜在治疗候选物。
