Renal Physiology Laboratory, Department of Physiology, Federal University of Paraná, Curitiba, State of Paraná, Brazil.
Laboratory of Neurophysiology, Department of Physiology, Federal University of Paraná, Curitiba, State of Paraná, Brazil.
Mol Cell Biochem. 2023 May;478(5):981-989. doi: 10.1007/s11010-022-04574-2. Epub 2022 Oct 6.
The focal segmental glomerulosclerosis (FSGS) is one of the most frequent glomerulopathy in the world, being considered a significative public health problem worldwide. The disease is characterized by glomerular loss mainly due to inflammation process and collagen fibers deposition. STAT-3 is a transcription factor associated with cell differentiation, migration and proliferation and in renal cells it has been related with fibrosis, acting on the progression of the lesion. Considering this perspective, the present study evaluated the involvement of STAT-3 molecule in an experimental model of FSGS induced by Doxorubicin (DOX). DOX mimics primary FSGS by causing both glomerular and tubular lesions and the inhibition of the STAT3 pathway leads to a decrease in fibrosis and attenuation of kidney damage. We described here a novel FSGS experimental model in a strain of genetically heterogeneous mice which resembles the reality of FSGS patients. DOX-injected mice presented elevated indices of albuminuria and glycosuria, that were significantly reduced in animals treated with a STAT-3 inhibitor (STATTIC), in addition with a decrease of some inflammatory molecules. Moreover, we detected that SOCS-3 (a regulator of STAT family) was up-regulated only in STATTIC-treated mice. Finally, histopathological analyzes showed that DOX-treated group had a significant increase in a tubulointerstitial fibrosis and tubular necrosis, which were not identified in both control and STATTIC groups. Thus, our results indicate that STAT-3 pathway possess an important role in experimental FSGS induced by DOX and may be an important molecule to be further investigated.
局灶节段性肾小球硬化症（FSGS）是世界上最常见的肾小球疾病之一，被认为是全球范围内一个重要的公共卫生问题。该疾病的特征是肾小球丢失，主要是由于炎症过程和胶原纤维沉积。STAT-3 是一种与细胞分化、迁移和增殖相关的转录因子，在肾细胞中与纤维化有关，参与病变的进展。考虑到这一观点，本研究评估了 STAT-3 分子在多柔比星（DOX）诱导的 FSGS 实验模型中的作用。DOX 通过引起肾小球和肾小管损伤来模拟原发性 FSGS，而 STAT-3 途径的抑制导致纤维化减少和肾脏损伤减轻。我们在这里描述了一种新的 FSGS 实验模型，该模型在一种遗传异质性的小鼠中具有与 FSGS 患者相似的特征。注射 DOX 的小鼠出现白蛋白尿和糖尿指数升高，而用 STAT-3 抑制剂（STATTIC）治疗的动物则显著降低，同时一些炎症分子也减少。此外，我们发现 SOCS-3（STAT 家族的一种调节剂）仅在 STATTIC 治疗的小鼠中上调。最后，组织病理学分析显示，DOX 处理组的肾小管间质纤维化和肾小管坏死显著增加，而在对照组和 STATTIC 组均未发现。因此，我们的结果表明，DOX 诱导的实验性 FSGS 中 STAT-3 途径具有重要作用，可能是一个有待进一步研究的重要分子。
