MDR1 gene polymorphisms and P-glycoprotein expression in respiratory diseases

Milojkovic, Maja; Milacic, Nena; Radović, Jelena; Ljubisavljević, Srdjan

doi:10.5507/bp.2014.032

Cited by 13 publications

(11 citation statements)

References 49 publications

(58 reference statements)

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“…et al, reporting the results of a meta-analysis, suggested that MDR C3435T and G2677A polymorphisms are associated with the risk of cancer, suggesting that different cytokines and chemokines involved in inflammation appear to be P-gp substrates, a potential cause of carcinogenesis (23). The importance of ABC transporters at tissue level has been studied especially in pulmonary neoplastic pathology (16,(39)(40)(41). Dogan et al suggested that MDR1 C3435T polymorphism may play a role in the occurance of chronic obstructive pulmonary disease through an inflamatory mechanism (40).…”

Section: Discussionmentioning

confidence: 99%

Association between MDR1 gene polymorphism and clinical course of pediatric pulmonary arterial hypertension

Muntean

Şuteu

Togănel

et al. 2018

Revista Romana De Medicina De Laborator

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Pulmonary arterial hypertension (PAH) is a progressive disease with a complex pathogenesis. The polymorphism of the gene of multidrug resistance-1 (MDR1) has been associated with many diseases including PAH. Objective. In this study we aimed to investigate the relevance of the MDR1 polymorphism to pediatric PAH clinical course. Methods. A total of 40 pediatric patients with PAH (secondary to congenital heart defects or idiopathic) and 40 control subjects were enrolled. Patients with PAH were divided into 2 groups, according to their evolution: 28 patients who remained clinically stable at 12-months (non-worsening group) and 12 patients who presented clinical worsening at 12-months (worsening group). Genomic DNA was genotyped for MDR1 gene polymorphisms as follows: C1236T, G2677T and C3435T. Results. There were no significant differences between PAH children groups (clinical worsening and non-worsening) nor between PAH children and controls in terms of frequency distribution of the three studied genotypes or alleles. Conclusions. The MDR1 polymorphism could not be correlated with the clinical evolution of pediatric PAH patients in our study.

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Section: Discussionmentioning

confidence: 99%

Association between MDR1 gene polymorphism and clinical course of pediatric pulmonary arterial hypertension

Muntean

Şuteu

Togănel

et al. 2018

Revista Romana De Medicina De Laborator

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“…ABC transporters (i.e., MRP1,P-gp), as an ATP-dependent pump, act as a gatekeeper against numerous xenobiotics, secretion of toxic compounds, apoptosis, and the immune response [ 24 , 25 ]. MRP1 is also associated with lung function and inflammatory markers in COPD patients [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Upregulation of Multidrug Resistance-Associated Protein 1 by Allyl Isothiocyanate in Human Bronchial Epithelial Cell: Involvement of c-Jun N-Terminal Kinase Signaling Pathway

Wang

et al. 2015

Oxidative Medicine and Cellular Longevity

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Multidrug resistance-associated protein 1 (MRP1) plays a protective role in the etiology and progression of chronic obstructive pulmonary disease (COPD) which results from oxidative stress and inflammation of lung injury. The lower functional MRP1 activity is related to COPD development. Our previous study showed that Allyl isothiocyanate (AITC) induced the expression and activity of MRP1 in a dose-dependent manner. However, which signaling pathway contributes to the upregulation of MRP1 by AITC is unclear. In this study, signaling pathway specific inhibitors were used to examine the mechanism of AITC. We found that JNK inhibitor SP600125 treatment decreased MRP1 mRNA expression in 16HBE14o- cells. But the ERK inhibitor U0126 or PI3K/Akt inhibitor LY294002 produced no obvious effect. The AITC-induced increase of MRP1 mRNA expression was abolished by cotreatment of SP600125, while it was not obviously affected by U0126 or LY294002. Furthermore, AITC acivates the JNK signaling pathway in 16HBE14o- cells. Finally, we found that JNK pathway mediated the upregulation of AITC-induced expression and function of MRP1. Taken together, our results indicated that AITC increased the expression and the activity of MRP1 via a JNK-dependent pathway. ERK and PI3K signaling pathway were not involved in the expression of MRP1 mRNA.

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“…Resistance to chemotherapy is associated with cancers that have high P-gp activity and these cancers also overexpress this membrane protein. 53 , 54 , 55 , 56 , 57 Despite extensive research, no P-gp modulator was capable of reducing chemotherapy resistance with acceptable side effects. 58 , 59 , 60 Poor responses were also found in the treatment of autoimmune and inflammatory bowel disease.…”

Section: P-gp Inhibition Therapymentioning

confidence: 99%

P‐glycoprotein and chronic rhinosinusitis

Miyake¹,

Nocera

Miyake³

2018

World j. otorhinolaryngol.-head neck surg.

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Chronic rhinosinusitis (CRS) is a heterogeneous definition that includes different disease states that usually are associated with abnormal inflammatory responses. Besides being prevalent, the mechanisms involved in its pathogenesis are not clear and there are few therapeutic options with tolerable side effects. P-glycoprotein (P-gp) is an efflux pump responsible of extruding xenobiotics and cellular metabolites from multiple cell types. It has been widely studied in the cancer field, due to its ability to confer resistance to chemotherapy. It also promotes Type 2 helper T-cell polarizing cytokine secretion in CRS and may represent a potential target to differentiate subtypes of CRS and personalize treatment. This state-of-the-art review explores current knowledge on the participation of P-gp in the pathogenesis of CRS, the P-gp inhibition as a novel targeted therapeutic strategy and the exosomal P-gp test, a non-invasive biomarker that can represent an important advance in the field of rhinology.

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MDR1 gene polymorphisms and P-glycoprotein expression in respiratory diseases

Cited by 13 publications

References 49 publications

Association between MDR1 gene polymorphism and clinical course of pediatric pulmonary arterial hypertension

Association between MDR1 gene polymorphism and clinical course of pediatric pulmonary arterial hypertension

Upregulation of Multidrug Resistance-Associated Protein 1 by Allyl Isothiocyanate in Human Bronchial Epithelial Cell: Involvement of c-Jun N-Terminal Kinase Signaling Pathway

P‐glycoprotein and chronic rhinosinusitis

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