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Fatty acid-binding protein 4 downregulation drives calcification in the development of kidney stone disease.
Kidney International ( IF 14.8 ) Pub Date : 2020-02-29 , DOI: 10.1016/j.kint.2020.01.042 Kazumi Taguchi 1 , Ling Chen 2 , Manint Usawachintachit 3 , Shuzo Hamamoto 4 , Misun Kang 2 , Teruaki Sugino 4 , Rei Unno 4 , David T Tzou 5 , Benjamin A Sherer 5 , Atsushi Okada 4 , Takahiro Yasui 4 , Sunita P Ho 2 , Marshall L Stoller 5 , Thomas Chi 5
Kidney International ( IF 14.8 ) Pub Date : 2020-02-29 , DOI: 10.1016/j.kint.2020.01.042 Kazumi Taguchi 1 , Ling Chen 2 , Manint Usawachintachit 3 , Shuzo Hamamoto 4 , Misun Kang 2 , Teruaki Sugino 4 , Rei Unno 4 , David T Tzou 5 , Benjamin A Sherer 5 , Atsushi Okada 4 , Takahiro Yasui 4 , Sunita P Ho 2 , Marshall L Stoller 5 , Thomas Chi 5
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Nephrolithiasis is a significant source of morbidity, and its incidence has increased significantly over the last decades. This rise has been attributed to concurrent increasing rates of obesity, associated with a 3-time risk of developing NL. To date, the mechanism by which obesity is linked to stone formation has not been elucidated. We aimed to utilize a transcriptomics approach to discover the missing link between these two epidemic diseases. We investigated gene expression profiling of nephrolithiasis patients by two RNA-sequencing approaches: comparison between renal papilla tissue with and without the presence of calcified Randall's plaques (RP), and comparison between the papilla, medulla, and cortex regions from within a single recurrent stone forming kidney. Results were overlaid between differently expressed genes found in the patient cohort and in the severely lithogenic kidney to identify common genes. Overlay of these two RNA-sequencing datasets demonstrated there is impairment of lipid metabolism in renal papilla tissue containing RP linked to downregulation of fatty acid binding protein (FABP) 4. Immunohistochemistry of human kidney specimens and microarray analysis of renal tissue from a nephrolithiasis mouse model confirmed that FABP4 downregulation is associated with renal stone formation. In a FABP4 knockout mouse model, FABP4 deficiency resulted in development of both renal and urinary crystals. Our study revealed that FABP4 plays an important, previously unrecognized role in kidney stone formation, providing a feasible mechanism to explain the link between nephrolithiasis and metabolic syndrome.
中文翻译：
脂肪酸结合蛋白 4 的下调驱动肾结石疾病发展中的钙化。
肾结石是发病率的重要来源，其发病率在过去几十年中显着增加。这种上升归因于肥胖率的同时增加，与发展为 NL 的 3 倍风险相关。迄今为止，肥胖与结石形成相关的机制尚未阐明。我们旨在利用转录组学方法来发现这两种流行病之间缺失的联系。我们通过两种 RNA 测序方法研究了肾结石患者的基因表达谱：比较存在和不存在钙化 Randall 斑块 (RP) 的肾乳头组织，以及比较单个复发性结石内的乳头、髓质和皮质区域形成肾。结果叠加在患者队列和严重致石性肾脏中发现的不同表达基因之间，以识别共同基因。这两个 RNA 测序数据集的叠加表明，含有 RP 的肾乳头组织中的脂质代谢受损与脂肪酸结合蛋白 (FABP) 的下调有关 4. 人肾标本的免疫组织化学和肾结石小鼠模型肾组织的微阵列分析证实FABP4下调与肾结石形成有关。在 FABP4 敲除小鼠模型中，FABP4 缺乏导致肾和尿晶体的发展。我们的研究表明，FABP4 在肾结石形成中起着重要的、以前未被认识的作用，
更新日期：2020-02-29
中文翻译：
脂肪酸结合蛋白 4 的下调驱动肾结石疾病发展中的钙化。
肾结石是发病率的重要来源，其发病率在过去几十年中显着增加。这种上升归因于肥胖率的同时增加，与发展为 NL 的 3 倍风险相关。迄今为止，肥胖与结石形成相关的机制尚未阐明。我们旨在利用转录组学方法来发现这两种流行病之间缺失的联系。我们通过两种 RNA 测序方法研究了肾结石患者的基因表达谱：比较存在和不存在钙化 Randall 斑块 (RP) 的肾乳头组织，以及比较单个复发性结石内的乳头、髓质和皮质区域形成肾。结果叠加在患者队列和严重致石性肾脏中发现的不同表达基因之间，以识别共同基因。这两个 RNA 测序数据集的叠加表明，含有 RP 的肾乳头组织中的脂质代谢受损与脂肪酸结合蛋白 (FABP) 的下调有关 4. 人肾标本的免疫组织化学和肾结石小鼠模型肾组织的微阵列分析证实FABP4下调与肾结石形成有关。在 FABP4 敲除小鼠模型中，FABP4 缺乏导致肾和尿晶体的发展。我们的研究表明，FABP4 在肾结石形成中起着重要的、以前未被认识的作用，
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