Overexpression of GRß in colonic mucosal cell line partly reflects altered gene expression in colonic mucosa of patients with inflammatory bowel disease

Nagy, Zsolt; Acs, Bence; Butz, Henriett; Feldman, Karolina; Marta, Alexa; Szabó, Péter M.; Baghy, Kornélia; Pazmany, Tamas; Rácz, Kàroly; Láng, István; Patócs, Attila

doi:10.1016/j.jsbmb.2015.10.006

Cited by 7 publications

(5 citation statements)

References 37 publications

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“…This resistance can be caused by its GRα antagonism as well as by the transcriptome changes its presence causes. A recent study showed that overexpression of GRβ in colonocytes causes dysregulation of many genes also found back in IBD patients (87). Next to GRα and GRβ, GRγ, GR-A, and GR-B splice variants have also been identified (illustrated in Figure 3).…”

Section: The Glucocorticoid Receptormentioning

confidence: 99%

A General Introduction to Glucocorticoid Biology

2019

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Glucocorticoids (GCs) are steroid hormones widely used for the treatment of inflammation, autoimmune diseases, and cancer. To exert their broad physiological and therapeutic effects, GCs bind to the GC receptor (GR) which belongs to the nuclear receptor superfamily of transcription factors. Despite their success, GCs are hindered by the occurrence of side effects and glucocorticoid resistance (GCR). Increased knowledge on GC and GR biology together with a better understanding of the molecular mechanisms underlying the GC side effects and GCR are necessary for improved GC therapy development. We here provide a general overview on the current insights in GC biology with a focus on GC synthesis, regulation and physiology, role in inflammation inhibition, and on GR function and plasticity. Furthermore, novel and selective therapeutic strategies are proposed based on recently recognized distinct molecular mechanisms of the GR. We will explain the SEDIGRAM concept, which was launched based on our research results.

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Section: The Glucocorticoid Receptormentioning

confidence: 99%

A General Introduction to Glucocorticoid Biology

2019

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“…This mechanism alters GRα signaling independent of GRα-GRβ heterodimer formation[ 58 ]. An in vitro study showed that overexpression of GRβ in a colonocyte cell model induces a vast deregulation of gene expression without Dex treatment, and a proportion of these genes have been shown to be altered in IBDs patients[ 59 ]. Thus, GRβ may directly change transcriptional gene activity of proinflammatory molecules.…”

Section: Molecular Basis Of Glucocorticoid Treatmentmentioning

confidence: 99%

Glucocorticosteroid therapy in inflammatory bowel diseases: From clinical practice to molecular biology

Dubois-Camacho

Ottum

Franco-Muñoz

et al. 2017

WJG

108

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Inflammatory bowel diseases (IBDs), such as ulcerative colitis and Crohn’s disease, are chronic pathologies associated with a deregulated immune response in the intestinal mucosa, and they are triggered by environmental factors in genetically susceptible individuals. Exogenous glucocorticoids (GCs) are widely used as anti-inflammatory therapy in IBDs. In the past, patients with moderate or severe states of inflammation received GCs as a first line therapy with an important effectiveness in terms of reduction of the disease activity and the induction of remission. However, this treatment often results in detrimental side effects. This downside drove the development of second generation GCs and more precise (non-systemic) drug-delivery methods. Recent clinical trials show that most of these new treatments have similar effectiveness to first generation GCs with fewer adverse effects. The remaining challenge in successful treatment of IBDs concerns the refractoriness and dependency that some patients encounter during GCs treatment. A deeper understanding of the molecular mechanisms underlying GC response is key to personalizing drug choice for IBDs patients to optimize their response to treatment. In this review, we examine the clinical characteristics of treatment with GCs, followed by an in depth analysis of the proposed molecular mechanisms involved in its resistance and dependence associated with IBDs. This thorough analysis of current clinical and biomedical literature may help guide physicians in determining a course of treatment for IBDs patients and identifies important areas needing further study.

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“…However, Kino et al, 2009 failed to observe any RU486-induced GRβ nuclear translocation. Three groups have recently shown that overexpression of GRβ affected mRNA expression positively and negatively in a gene-specific fashion, suggesting that that GRβ has its own intrinsic transcriptional activities independent of GRα (Kino et al, 2009; Lewis-Tuffin et al; 2007, and Nagy et al, 2016). Nevertheless, this could be due to dimerization with other receptors or transcription factors.…”

Section: Mechanisms That Control Levels Of Gcsmentioning

confidence: 99%

Glucocorticoid therapy and ocular hypertension

Dibas

Yorio

2016

European Journal of Pharmacology

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The projected number of people who will develop age-related macular degeneration in estimated at 2020 is 196 million and is expected to reach 288 million in 2040. Also, the number of people with Diabetic retinopathy will grow from 126.6 million in 2010 to 191.0 million by 2030. In addition, it is estimated that there are 2.3 million people suffering from uveitis worldwide. Because of the anti-inflammatory properties of glucocorticoids (GCs), they are often used topically and/or intravitreally to treat ocular inflammation conditions or edema associated with macular degeneration and diabetic retinopathy. Unfortunately, ocular GC therapy can lead to severe side effects. Serious and sometimes irreversible eye damage can occur as a result of the development of GC-induced ocular hypertension causing secondary open-angle glaucoma. According to the world health organization, glaucoma is the second leading cause of blindness in the world and it is estimated that 80 million will suffer from glaucoma by 2020. In the current review, mechanisms of GC-induced damage in ocular tissue, GC-resistance, and enhancing GC therapy will be discussed.

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Overexpression of GRß in colonic mucosal cell line partly reflects altered gene expression in colonic mucosa of patients with inflammatory bowel disease

Cited by 7 publications

References 37 publications

A General Introduction to Glucocorticoid Biology

A General Introduction to Glucocorticoid Biology

Glucocorticosteroid therapy in inflammatory bowel diseases: From clinical practice to molecular biology

Glucocorticoid therapy and ocular hypertension

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