STRA6与妊娠期糖尿病中的胎盘类维生素A代谢

STRA6 and Placental Retinoid Metabolism in Gestational Diabetes Mellitus.

作者信息

Fruscalzo Arrigo, Viola Luigi, Orsaria Maria, Marzinotto Stefania, Bulfoni Michela, Driul Lorenza, Londero Ambrogio P, Mariuzzi Laura

机构信息

Clinic of Obstetrics and Gynecology, University Hospital of Fribourg, 1708 Fribourg, Switzerland.

Clinic of Radiology, University Federico II, 80138 Naples, Italy.

出版信息

J Pers Med. 2021 Dec 5;11(12):1301. doi: 10.3390/jpm11121301.

DOI:10.3390/jpm11121301

PMID:34945773

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8708334/

Abstract

BACKGROUND

Recent reports indicate the potential role of the stimulated by retinoic acid 6 (STRA6) protein in developing insulin resistance. The study's objective was to assess placental STRA6 expression and staining pattern in human pregnancy complicated by gestational diabetes mellitus (GDM). The expression pattern of further relevant genes involved in retinoid metabolism was also evaluated.

METHODS

A retrospective case-control study on paraffin-embedded placental tissue. Twenty-two human pregnancies affected by GDM, namely, 11 insulin-treated (iGDM) and 11 diet-controlled (dGDM), were compared with 22 normal-developed pregnancies (controls). An RT-PCR was performed in a random sample of 18 patients (six iGDM, six dGDM, and six controls) to assess RNA expression of STRA6 and further markers of retinoid metabolism. A semi-quantitative intensity evaluation at immunohistochemistry was performed for STRA6 in all 44 recruited patients.

RESULTS

STRA6 showed a decreased placental staining (9.09% vs. 68.18% positively stained samples, < 0.05) and augmented RNA expression in dGDM patients than controls (ΔCT expression 0.473, IQR 0.403-0.566 vs. 0.149, IQR 0.092-0.276, < 0.05). The protein staining pattern in patients affected by iGDM was comparable to controls. A reduced RNA expression of LPL, LRP1, VLDLR, and MTTP besides an augmented expression of LDLR was found in dGDM, while overexpression of LRP1 and LPL was found in iGDM patients. Unlike in the control group, significant positive correlations were found between RXRα and the proteins involved in the intracellular uptake of ROH, such as STRA6, LRP1, LRP2, and VLDLR.

CONCLUSIONS

An altered placental expression and staining pattern of STRA6 were found in pregnancies complicated by GDM compared to the controls. These changes were coupled to an altered expression pattern of several other genes involved in the retinoid metabolism.

摘要

背景

近期报告表明视黄酸刺激蛋白6（STRA6）在胰岛素抵抗发生发展中可能发挥作用。本研究的目的是评估妊娠期糖尿病（GDM）合并妊娠时胎盘STRA6的表达及染色模式。还评估了参与类维生素A代谢的其他相关基因的表达模式。

方法

对石蜡包埋的胎盘组织进行回顾性病例对照研究。将22例受GDM影响的妊娠，即11例接受胰岛素治疗的（iGDM）和11例饮食控制的（dGDM），与22例正常发育的妊娠（对照组）进行比较。对18例患者（6例iGDM、6例dGDM和6例对照）的随机样本进行逆转录聚合酶链反应（RT-PCR），以评估STRA6及类维生素A代谢的其他标志物的RNA表达。对所有44例纳入患者的STRA6进行免疫组织化学半定量强度评估。

结果

与对照组相比，dGDM患者胎盘STRA6染色减少（阳性染色样本9.09%对68.18%，P<0.05），RNA表达增加（ΔCT表达0.473，四分位数间距0.403 - 0.566对0.149，四分位数间距0.092 - 0.276，P<0.05）。iGDM患者的蛋白染色模式与对照组相当。dGDM患者中脂蛋白脂肪酶（LPL）、低密度脂蛋白受体相关蛋白1（LRP1）、极低密度脂蛋白受体（VLDLR）和微粒体甘油三酯转运蛋白（MTTP）的RNA表达降低，而低密度脂蛋白受体（LDLR）表达增加，iGDM患者中LRP1和LPL过表达。与对照组不同，在视黄酸X受体α（RXRα）与参与视黄醇细胞内摄取的蛋白（如STRA6、LRP1、LRP2和VLDLR）之间发现显著正相关。