Clinicopathological Relevance of PAX8 Expression Patterns in Acute Kidney Injury and Chronic Kidney Diseases.

Clinicopathological Relevance of PAX8 Expression Patterns in Acute Kidney Injury and Chronic Kidney Diseases.
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DOI:
10.3390/diagnostics12092036
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发表时间:
2022-08-23
期刊:
影响因子:
3.6
通讯作者:
Ostojic, Jelena Nesovic
Ostojic, Jelena Nesovic
中科院分区:
医学3区
文献类型:
--
作者:
Zivotic, Maja;Dundjerovic, Dusko;Naumovic, Radomir;Kovacevic, Sanjin;Ivanov, Milan;Karanovic, Danijela;Nikolic, Gorana;Markovic-Lipkovski, Jasmina;Skodric, Sanja Radojevic;Ostojic, Jelena Nesovic

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转录因子PAX8在胚胎肾发育过程中表达,先前已在各种肾脏肿瘤中检测到。为了研究PAX8转录因子在急性肾损伤(阿基)和慢性肾脏病(CKD)中的表达,进行免疫组织化学分析。在31个阿基的人肾样品(25个尸检病例,5个病因不明的肾活检和1个确诊肌红蛋白管型肾病的阿基)以及诱导缺血后阿基的动物中分析PAX8表达的存在、位置和程度。此外,在20例CKD肾活检样本中分析了表达模式。我们的研究表明,各种肾脏疾病的慢性疾病过程中,导致肾小管萎缩和间质纤维化的形成,导致PAX8表达在近端小管的细胞核。此外,将仔细监测在受损近端小管内检测到PAX8的患者,因为在随访期间观察到肾功能恶化。我们还发现,肌红蛋白引起急性肾损伤,随后出现大范围的肾损伤,与近端肾小管细胞中PAX8的强核表达有关。这些结果得到了支持,其次是在诱导缺血后急性肾损伤的实验模型中获得的数据。考虑到这些发现,我们可以假设PAX8蛋白可能参与急性肾损伤后的再生过程和恢复。因此,相应地,所有关于PAX8免疫标记的研究都应该在活个体的活检样品上进行。
Transcription factor PAX8, expressed during embryonic kidney development, has been previously detected in various kidney tumors. In order to investigate expression of PAX8 transcription factor in acute kidney injury (AKI) and chronic kidney diseases (CKD), immunohistochemical analysis was performed. Presence, location and extent of PAX8 expression were analyzed among 31 human kidney samples of AKI (25 autopsy cases, 5 kidney biopsies with unknown etiology and 1 AKI with confirmed myoglobin cast nephropathy), as well as in animals with induced postischemic AKI. Additionally, expression pattern was analyzed in 20 kidney biopsy samples of CKD. Our study demonstrates that various kidney diseases with chronic disease course that results in the formation of tubular atrophy and interstitial fibrosis, lead to PAX8 expression in the nuclei of proximal tubules. Furthermore, patients with PAX8 detected within the damaged proximal tubuli would be carefully monitored, since deterioration in kidney function was observed during follow-up. We also showed that myoglobin provoked acute kidney injury followed with large extent of renal damage, was associated with strong nuclear expression of PAX8 in proximal tubular cells. These results were supported and followed by data obtained in experimental model of induced postischemic acute kidney injury. Considering these findings, we can assume that PAX8 protein might be involved in regeneration process and recovery after acute kidney injury. Thus, accordingly, all investigation concerning PAX8 immunolabeling should be performed on biopsy samples of the living individuals.
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