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IgA 肾病患者组中组蛋白去乙酰化酶 6 的表达与临床参数的相关性分析。

Correlation analysis between expression of histone deacetylase 6 and clinical parameters in IgA nephropathy patients.

机构信息

Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Ren Fail. 2021 Dec;43(1):684-697. doi: 10.1080/0886022X.2021.1914657.

DOI:10.1080/0886022X.2021.1914657
PMID:33896334
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8079031/
Abstract

BACKGROUND

It has been demonstrated that histone deacetylase 6 (HDAC6) is involved in various kidney diseases in experimental study. However, correlation between HDAC6 and clinical parameters in IgA nephropathy (IgAN) patients is still unknown.

METHODS

A total of 46 human kidney biopsy specimens with IgAN were selected as observation group, specimens of normal renal cortex tissue that was not affected by the tumor from patients with renal carcinoma ( = 7) served as control. We investigated the relationship between HDAC6 and clinical parameters in IgAN.

RESULTS

HDAC6 was highly expressed in human kidney biopsy specimens with IgAN compared with control group, while the number of acetyl histone H3 positive cells were significantly decreased. There was a statistical difference in the indexes of albumin, estimated glomerular filtration rate (eGFR), serum urea, serum creatinine, serum uric acid, β2-microglobulin, cystatin C, cholesterol, high-density lipoprotein, low-density lipoprotein, and HDAC6 positive area among the different Oxford Classification ( < 0.05). The expression of HDAC6 was different in various eGFR levels, the expression of HDAC6 increased with the decreasing of eGFR level, the expression of acetyl histone H3 decreased with the decreasing of eGFR level. In addition, the expression of HDAC6 positively correlated with Masson trichrome positive area, serum urea, serum creatinine, β2 macroglobulin, and cystatin C, while negatively correlated with eGFR and acetyl histone H3. Multivariate linear regression analysis demonstrated that eGFR and cystatin C were independently associated with HDAC6, respectively ( < 0.05).

CONCLUSIONS

These results suggested that high level of HDAC6 expression in IgAN is correlated with renal dysfunction.

摘要

背景

已有研究表明组蛋白去乙酰化酶 6(HDAC6)参与多种肾脏疾病。然而,HDAC6 与 IgA 肾病(IgAN)患者临床参数的相关性尚不清楚。

方法

选取 46 例经肾活检证实的 IgAN 患者作为观察组,另取同期因肾癌行根治性肾切除患者的正常肾皮质组织(未受肿瘤累及)作为对照组。观察 HDAC6 与 IgAN 患者临床参数的关系。

结果

观察组 HDAC6 蛋白表达水平较对照组显著升高,而组蛋白 H3 乙酰化阳性细胞数明显减少。不同牛津病理分级( < 0.05)患者的白蛋白、估算肾小球滤过率(eGFR)、血清尿素、血清肌酐、血清尿酸、β2 微球蛋白、胱抑素 C、胆固醇、高密度脂蛋白、低密度脂蛋白以及 HDAC6 阳性面积等指标存在统计学差异。不同 eGFR 水平患者的 HDAC6 表达水平存在差异,随着 eGFR 水平的降低,HDAC6 表达逐渐增加,组蛋白 H3 乙酰化表达逐渐减少。此外,HDAC6 的表达与 Masson 三色染色阳性面积、血清尿素、血清肌酐、β2 微球蛋白、胱抑素 C 呈正相关,与 eGFR 和组蛋白 H3 乙酰化呈负相关。多元线性回归分析表明,eGFR 和胱抑素 C 与 HDAC6 分别独立相关( < 0.05)。

结论

这些结果表明,IgAN 中 HDAC6 的高表达与肾功能不全有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e845/8079031/23c508a8da65/IRNF_A_1914657_F0006_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e845/8079031/e8ea134f6dfe/IRNF_A_1914657_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e845/8079031/f3c7c1d447a3/IRNF_A_1914657_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e845/8079031/7484ab31aa4c/IRNF_A_1914657_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e845/8079031/ad973e90baec/IRNF_A_1914657_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e845/8079031/ecc65b6c4dc5/IRNF_A_1914657_F0005_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e845/8079031/23c508a8da65/IRNF_A_1914657_F0006_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e845/8079031/e8ea134f6dfe/IRNF_A_1914657_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e845/8079031/f3c7c1d447a3/IRNF_A_1914657_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e845/8079031/7484ab31aa4c/IRNF_A_1914657_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e845/8079031/ad973e90baec/IRNF_A_1914657_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e845/8079031/ecc65b6c4dc5/IRNF_A_1914657_F0005_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e845/8079031/23c508a8da65/IRNF_A_1914657_F0006_B.jpg

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Histone deacetylase 6 inhibition mitigates renal fibrosis by suppressing TGF-β and EGFR signaling pathways in obstructive nephropathy.组蛋白去乙酰化酶 6 抑制通过抑制 TGF-β和 EGFR 信号通路减轻梗阻性肾病中的肾纤维化。
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