Renal fibrosis is a common pathological manifestation of almost all forms of kidney disease irrespective of the etiological cause. Microvascular rarefaction represents itself as an important phenomenon associated with renal fibrosis and shows strong correlation with decline in renal functions. Lysyl oxidase (LOX) catalyzes crosslinking of extracellular matrix (ECM) proteins including collagens, plays an important role in stabilization of degradation resistant matrix. Since, there seems to be a causal link between deposition of excessive ECM and microvascular rarefaction, we investigated the effects of reduction in renal fibrosis on microvascular rarefaction in acute as well as end stage kidney. We used a well-established unilateral ureteral obstruction (UUO)-induced renal fibrosis model to produce renal fibrosis in animals. We treated animals with a LOX inhibitor, β-aminopropionitrile (BAPN, 100 mg/kg, i.p.) and investigated effects on renal fibrosis and microvascular rarefaction. We observed that LOX inhibition was associated with reduction in collagen deposition in UUO-induced renal fibrosis animal model. Further, ECM normalization by LOX inhibition decreased the loss of peritubular capillaries (PTCs) in fibrotic kidney in acute study while the LOX inhibition failed to inhibit PTCs loss in end stage kidney. The results of present study suggested that inhibition of LOX reduces collagen deposition and renal fibrosis. Further, the reduction in fibrosis fails to protect from PTCs loss in chronic study suggesting the absence of strong link between reduction in fibrosis and improvement in PTCs in an end stage kidney.

中文翻译：

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赖氨酰氧化酶的抑制通过抑制 CD44 介导的周细胞脱离和管周毛细血管损失来改善肾损伤


肾纤维化是几乎所有形式的肾脏疾病的常见病理表现，无论病因如何。微血管稀疏本身是与肾纤维化相关的重要现象，并且与肾功能下降密切相关。赖氨酰氧化酶 (LOX) 催化包括胶原蛋白在内的细胞外基质 (ECM) 蛋白的交联，在稳定抗降解基质方面发挥着重要作用。由于过量 ECM 沉积与微血管稀疏之间似乎存在因果关系，因此我们研究了肾纤维化减少对急性和终末期肾脏微血管稀疏的影响。我们使用完善的单侧输尿管梗阻（UUO）诱导的肾纤维化模型在动物中产生肾纤维化。我们用 LOX 抑制剂 β-氨基丙腈（BAPN，100 mg/kg，腹腔注射）治疗动物，并研究其对肾纤维化和微血管稀疏的影响。我们观察到，在 UUO 诱导的肾纤维化动物模型中，LOX 抑制与胶原沉积减少相关。此外，在急性研究中，通过LOX抑制使ECM正常化减少了纤维化肾脏中管周毛细血管（PTC）的损失，而LOX抑制未能抑制终末期肾脏中的PTC损失。本研究结果表明，抑制 LOX 可减少胶原沉积和肾纤维化。此外，长期研究表明，纤维化的减少并不能防止 PTC 损失，这表明纤维化的减少与终末期肾脏中 PTC 的改善之间不存在紧密联系。