Amity Institute of Biotechnology, Amity University Uttar Pradesh Lucknow, Sanjay Gandhi Post Graduate Institute f Medical Sciences, Lucknow, India.
Department of Pulmonary Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Uttar Pradesh, India.
Curr Pharm Biotechnol. 2021;22(3):408-413. doi: 10.2174/1389201021666200529104042.
Resistance to corticosteroid is an essential mechanism in uncontrolled asthma as the corticosteroid is the mainstay of therapy. There are recent reports that epigenetic factors play a crucial role in the regulation of steroid action. Overexpression of P glycoprotein (P-gp) and reduced expression of Histone Deacetylase 2 (HDAC2) have been linked to regulating the steroid action in other diseases like Nephrotic Syndrome (NS). However, their role in uncontrolled asthma is still not clear and warrants further investigation. We evaluated the expression and activity of P-gp and HDAC2 in patients with Controlled Asthma (CA) and Uncontrolled Asthma (UA).
A total of 60 CA (mean age 51.72±17.02 years, male=38), and 38 of UA (mean age=53.55±11.90 years, male=17) were recruited. The level of control was defined according to (Global Initiative for Asthma) GINA 2016 criteria. The mRNA expression of HDAC2 and P-gp was studied by quantitative real-time Polymerase Chain Reaction (PCR), the functional activity of P-gp was evaluated by a commercially available kit via flow cytometry, and HDAC2 enzymatic activity was measured by commercially available kit by Enzyme-Linked Immunosorbent Assay (ELISA).
P-gp expression and the functionality were significantly higher in the UA group of patients as compared to the CA group of patients (p<0.005), moreover HDAC2 expression was significantly reduced in UA patients as compared to CA patients, (p<0.005). The enzymatic activity of HDAC2 was also significantly reduced in UA patients as compared to CA patients (p<0.005).
P-gp overexpression and HDAC2 under expression play an essential role in uncontrolled asthma by impairing the response to corticosteroid.
在未得到控制的哮喘中，对抗皮质类固醇是一种基本机制，因为皮质类固醇是治疗的主要手段。最近有报道称，表观遗传因素在调节类固醇作用中起着至关重要的作用。在其他疾病如肾病综合征（NS）中，P 糖蛋白（P-gp）的过度表达和组蛋白去乙酰化酶 2（HDAC2）的表达降低与调节类固醇作用有关。然而，它们在未得到控制的哮喘中的作用尚不清楚，需要进一步研究。我们评估了在得到控制的哮喘（CA）和未得到控制的哮喘（UA）患者中 P-gp 和 HDAC2 的表达和活性。
共招募了 60 名 CA（平均年龄 51.72±17.02 岁，男性=38）和 38 名 UA（平均年龄=53.55±11.90 岁，男性=17）患者。根据（全球哮喘倡议）GINA 2016 标准定义控制水平。通过定量实时聚合酶链反应（PCR）研究 HDAC2 和 P-gp 的 mRNA 表达，通过流式细胞术评估商业试剂盒中 P-gp 的功能活性，通过酶联免疫吸附试验（ELISA）用商业试剂盒测量 HDAC2 的酶活性。
与 CA 组患者相比，UA 组患者的 P-gp 表达和功能显著更高（p<0.005），此外，UA 患者的 HDAC2 表达也明显低于 CA 患者（p<0.005）。与 CA 患者相比，UA 患者的 HDAC2 酶活性也明显降低（p<0.005）。
P-gp 过度表达和 HDAC2 表达降低在未得到控制的哮喘中起着重要作用，通过损害对皮质类固醇的反应。
