Transforming growth factor beta1 targets estrogen receptor signaling in bronchial epithelial cells

Smith, L. Cody; Moreno, Santiago; Robertson, Lauren; Robinson, Sarah; Gant, Kristal; Bryant, Andrew J.; Sabo‐Attwood, Tara

doi:10.1186/s12931-018-0861-5

Cited by 39 publications

(26 citation statements)

References 94 publications

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“…70 The activation of the ERs can modulate pro-inflammatory cytokines due to inhibition of NF-κB, an important nuclear factor for cellular signaling, limiting the severity of the inflammation. 71,72 In ARDS, one of the severe complications of COVID-19, experimental studies have suggested a protective role of estrogen. Rats submitted to acute lung injury induced by seawater aspiration have pulmonary edema reductions by downregulation of aquaporins after the administration of 17β-estradiol.…”

Section: Estrogen Role In Lung Inflammationmentioning

confidence: 99%

SARS‐CoV‐2 and the possible connection to ERs, ACE2, and RAGE: Focus on susceptibility factors

et al. 2020

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has provoked major stresses on the health-care systems of several countries, and caused the death of more than a quarter of a million people globally, mainly in the elderly population with preexisting pathologies. Previous studies with coronavirus (SARS-CoV) point to gender differences in infection and disease progression with increased susceptibility in male patients, indicating that estrogens may be associated with physiological protection against the coronavirus. Therefore, the objectives of this work are threefold. First, we aim to summarize the SARS-CoV-2 infection pathway and the roles both the virus and patient play in COVID-19 (Coronavirus disease 2019) progression, clinical symptomatology, and mortality. Second, we detail the effect estrogen has on viral infection and host infection response, including its role in both the regulation of key viral receptor expression and the mediation of inflammatory activity. Finally, we describe how ERs (estrogen receptors) and RAGE (receptor for advanced glycation end-products) play a critical role in metabolic pathways, which we 14104 | STILHANO eT AL. 1 | INTRODUCTION 1.1 | SARS-CoV-2 and COVID-19 Coronavirus disease 2019 (COVID-19) is a disease caused by the new coronavirus called SARS-CoV-2 (SARScoronavirus 2). In December 2019, the first case of COVID-19 was diagnosed in the city of Wuhan, China. 1 The virus disseminated rapidly and the World Health Organization (WHO) declared SARS-CoV-2 as a pandemic on March 11th 2020, given that it had already spread to more than 188 countries on five continents. Updated epidemiological data from the Johns Hopkins University indicator shows that there are more than 20 million cases and over 730 thousand deaths due to COVID-19 by the beginning of August 2020 (https://coron avirus.jhu.edu/map.html-accessed on August 11, 2020 14:00 GMT). The Case Fatality Rate (CFR) for COVID-19 increases exponentially with age. 2,3 For example, for patients aged between 65 and 74 years old, the CFR is 3%-5%, 4%-11% CFR for 75 and 84 years old and 10%-27% CFR for the patients above 85 years old. 2 Obesity, diabetes, and hypertension are comorbidities associated with increased risk for developing the severe form of COVID-19. Data attributed to the Centers for Disease Control and Prevention (https://www.cdc.gov/coron aviru s/2019-ncov/need-extra preca ution s/group sat -highe r-risk. html) shows that diabetes is one of the major risk factors for fatal outcomes from COVID-19. Considering that diabetic patients usually have hyperglycemia, impaired immune function, and several comorbidities such as hypertension, dyslipidemia, and cardiovascular disease, this group is more susceptible to be severely infected by SARS-CoV-2. 4 Another important risk for fatal COVID-19 is obesity, particularly in males. 5,6 Moreover, COVID-19 also affects more severely individuals with metabolic syndrome, probably because these patients have a pro-inflammatory condition that may contribute to enhance...

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Section: Estrogen Role In Lung Inflammationmentioning

confidence: 99%

SARS‐CoV‐2 and the possible connection to ERs, ACE2, and RAGE: Focus on susceptibility factors

et al. 2020

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“…100 On the other hand, a recent study reported that transforming growth factor beta1 (TGF-b1) represses the expression of ERa in bronchial epithelial cells. 65 There are two classes of ERs: the nuclear ERs: ERa (ESR1) and ERb (ESR2), and the membrane ERs: mERs (G protein-coupled ER 1, GPER/GPER30). 101 Estrogen directly binds to the nuclear ERs, triggering receptor dimerization and binding to estrogen response elements (EREs) in the promoter region of target genes.…”

Section: Estrogenmentioning

confidence: 99%

Endocrine regulation of lung disease and inflammation

Fuentes

Silveyra

2018

Exp Biol Med (Maywood)

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Sex-based disparities have been identified in respiratory physiology, and in many chronic lung diseases including asthma, chronic obstructive pulmonary disease, and cystic fibrosis. The observed sex differences in lung disease prevalence and incidence have been linked to changes in circulating levels of sex hormones that start after puberty and that have been shown to affect physiological and immunological functions. While the exact roles of male and female sex hormones in these processes have not been fully elucidated, it is now evident that these can target many lung cell types and affect several functions of the respiratory system. In this mini-review, we have summarized seminal studies aimed to understand the effects of the most relevant male and female sex hormones (estrogens, progesterone, and androgens) and their receptors on lung function. Moreover, we have reviewed the known influences of sex hormones and of the hypothalamic–pituitary–gonadal axis in lung disease and immunity. Understanding the roles of sex hormones in the regulation of lung function and inflammation is the first step for the potential development of more effective therapeutic options to prevent and treat lung disease in men and women. Impact statement Sex-differences in the incidence and severity of inflammatory lung diseases have been recognized for years. Women of reproductive age are more likely to suffer from chronic lung disease, with higher mortality rates than men. Physiological changes in hormone levels such as those occurring during the menstrual cycle, pregnancy, and menopause have been associated with lung function changes and asthma symptoms. Despite this, the roles of sex hormones in the mechanisms associated with lung diseases have not been fully elucidated. This review summarizes basic and clinical studies of sex hormones as potential modulators of lung function and inflammation. The information obtained from sex-specific research on lung physiology and pathology will potentially help in the development of sex-specific therapeutics for inflammatory lung disease that may account for the hormonal status of the patient.

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“…[6] In bronchial epithelial cells, estrogen and transforming growth factor beta1 have been shown to inversely modulate the expression of several genes involved in extracellular matrix turnover, airway smooth muscle cell contraction, and calcium flux regulation. [7] Adipose tissue accounts for the majority of peripheral estrogen synthesis and its contribution to the circulating pool of estrogens increases with body mass and age. [17] It has been shown that bariatric surgery in women can lead to significant decreases in estradiol, total testosterone, and dehydroepiandrosterone sulfate (DHEA-S) as well as significant increases in follicle stimulating hormone, luteinizing hormone, and sex hormone binding globulin.…”

Section: Discussionmentioning

confidence: 99%

“…Obesity can be both a consequence of sarcoidosis treatment and a contributor to disease risk likely through the pro-inflammatory environment of obesity. [5] Although the etiology of sarcoidosis progression is still largely unknown, recent studies propose a role for sex hormones [6][7][8][9] and the microbiome in the pathogenesis of fibrotic lung disease. [10][11][12] These gaps in knowledge limit the identification of effective treatments.…”

Section: Introductionmentioning

confidence: 99%

Improvement of pulmonary sarcoidosis following sleeve gastrectomy

Hassell¹,

Grzeszczak²,

Adams³

et al. 2019

CRIM

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Pulmonary sarcoidosis is unlikely to resolve if it persists for greater than five years. A growing body of literature supports the involvement of the microbiome in sarcoidosis and a role for sex hormones in pulmonary fibrosis. Additionally, obesity is a risk factor for the development of sarcoidosis. Bariatric surgery is an effective treatment for obesity and can lead to microbial and endocrine changes. Here, we report the clinical improvement of longstanding pulmonary sarcoidosis following sleeve gastrectomy.

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Transforming growth factor beta1 targets estrogen receptor signaling in bronchial epithelial cells

Cited by 39 publications

References 94 publications

SARS‐CoV‐2 and the possible connection to ERs, ACE2, and RAGE: Focus on susceptibility factors

SARS‐CoV‐2 and the possible connection to ERs, ACE2, and RAGE: Focus on susceptibility factors

Endocrine regulation of lung disease and inflammation

Improvement of pulmonary sarcoidosis following sleeve gastrectomy

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