Estrogen Signaling and MicroRNAs in Lung Fibrosis. Sex, Hormones, and Rock Scars.
Ontology highlight
ABSTRACT:
SUBMITTER: Tzouvelekis A
PROVIDER: S-EPMC6857495 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:MicroRNAs are implicated in many biological and pathological processes and are emerging as key actors in lung health and disease. Specific patterns of dysregulated microRNAs have been found in idiopathic pulmonary fibrosis (IPF), an untreatable interstitial lung disease of unknown etiology. IPF is characterized by dramatic and extensive phenotypic changes in the lung that include alveolar cell hyperplasia, fibroblast proliferation and formation of myofibroblast foci, deposition of extracellular matrix, and changes in lung transcriptional programming. Here, we discuss the latest insights about the role of microRNAs in lung fibrosis with a focus on the contribution of animal models of disease to the derivation of these insights.
| S-EPMC4201640 | biostudies-literature
Project description:The importance of sex hormones, especially estrogen, in the pathogenesis of non-small-cell lung cancer (NSCLC) has attracted attention due to its high incidence among young adults and nonsmokers, especially those who are female. Cancer-associated fibroblasts (CAFs) reside in the cancer stroma and influence cancer growth, invasion, metastasis, and acquisition of drug resistance through interactions with cancer cells and other microenvironmental components. Hormone-mediated cell-cell interactions are classic cell-cell interactions and well-known phenomena in breast cancer and prostate cancer CAFs. In cancers of other organs, including NSCLC, the effects of CAFs on hormone-receptor expression and hormone production in cancer tissues have been reported; however, there are few such studies. Many more studies have been performed on breast and prostate cancers. Recent advances in technology, particularly single-cell analysis techniques, have led to significant advances in the classification and function of CAFs. However, the importance of sex hormones in cell-cell interactions of CAFs in NSCLC remains unclear. This review summarizes reports on CAFs in NSCLC and sex hormones in cancer and immune cells surrounding CAFs. Furthermore, we discuss the prospects of sex-hormone research involving CAFs in NSCLC.
| S-EPMC10377312 | biostudies-literature
Project description:The main mechanisms underlying sexually dimorphic outcomes in neonatal lung injury are unknown. We tested the hypothesis that hormone- or sex chromosome-mediated mechanisms interact with hyperoxia exposure to impact injury and repair in the neonatal lung. To distinguish sex differences caused by gonadal hormones versus sex chromosome complement (XX versus XY), we used the Four Core Genotypes (FCG) mice and exposed them to hyperoxia (95% FiO2, P1-P4: saccular stage) or room air. This model generates XX and XY mice that each have either testes (with Sry, XXM, or XYM) or ovaries (without Sry, XXF, or XYF). Lung alveolarization and vascular development were more severely impacted in XYM and XYF compared with XXF and XXM mice. Cell cycle-related pathways were enriched in the gonadal or chromosomal females, while muscle-related pathways were enriched in the gonadal males, and immune-response-related pathways were enriched in chromosomal males. Female gene signatures showed a negative correlation with human patients who developed bronchopulmonary dysplasia (BPD) or needed oxygen therapy at 28 days. These results demonstrate that chromosomal sex - and not gonadal sex - impacted the response to neonatal hyperoxia exposure. The female sex chromosomal complement was protective and could mediate sex-specific differences in the neonatal lung injury.
| S-EPMC8410054 | biostudies-literature
Project description:This study was conducted in neonatal FCG male and female neonatal mice.
2021-09-14 | GSE162853 | GEO
Project description:Background and objectiveIPF is an ageing-related lung disorder featuring progressive lung scarring. IPF patients are frequently identified with short telomeres but coding mutations in telomerase can only explain a minority of cases. Sex hormones regulate telomerase activity in vitro and levels of sex hormones are related to LTL. The objective of this study was to explore whether sex hormones were associated with LTL, whether they interacted with genetic variants in telomerase and whether polymorphisms in the exon of androgen metabolism genes were associated with plasma testosterone concentrations in male IPF patients.MethodsA case-control study was performed on 101 male IPF subjects and 51 age-matched healthy controls. Early morning plasma sex hormones were quantified, and whole-exome sequencing was used to identify rare protein-altering variants of telomerase and SNP in the exon of androgen metabolism genes. LTL was analysed by PCR and expressed as a T/S ratio.ResultsLTL, testosterone and DHT were decreased significantly in the IPF group. After adjustments for age and variant status in telomerase-related genes, only testosterone was positively associated with LTL (P = 0.001). No significant interaction (P = 0.661) was observed between rare protein-altering variants of telomerase and testosterone. No coding SNP in androgen metabolism genes were significantly associated with testosterone concentrations.ConclusionPlasma testosterone is associated with LTL independent of age or rare protein-altering variants of telomerase. No genetic variations of androgen-related pathway genes are associated with androgen concentrations. Further studies are warranted to examine whether hormonal interventions might retard telomere loss in male IPF patients.
| S-EPMC7754418 | biostudies-literature
Project description:Despite being a crucial physiological function of the brain, the mechanisms underlying forgetting are still poorly understood. Estrogens play a critical role in different brain functions, including memory. However, the effects of sex hormones on forgetting vulnerabilitymediated by retroactive interference (RI), a phenomenon in which newly acquired information interferes with the retrieval of already stored information, are still poorly understood. The aim of our study was to characterize the sex differences in interference-mediated forgetting and identify the underlying molecular mechanisms. We found that adult male C57bl/6 mice showed a higher susceptibility to RI-dependent memory loss than females. The preference index (PI) in the NOR paradigm was 52.7 ± 5.9% in males and 62.3 ± 13.0% in females. The resistance to RI in female mice was mediated by estrogen signaling involving estrogen receptor α activation in the dorsal hippocampus. Accordingly, following RI, females showed higher phosphorylation levels (+30%) of extracellular signal-regulated kinase1/2 (ERK1/2) in the hippocampus. Pharmacological inhibition of ERK1/2 made female mice prone to RI. The PI was 70.6 ± 11.0% in vehicle-injected mice and 47.4 ± 10.8% following PD98059 administration. Collectively, our data suggest that hippocampal estrogen α receptor-ERK1/2 signaling is critically involved in a pattern separation mechanism that inhibits object-related RI in female mice.
| S-EPMC9219958 | biostudies-literature
Project description:Hearing loss is the most common form of sensory impairment in humans, with an anticipated rise in incidence as the result of recreational noise exposures. Hearing loss is also the second most common health issue afflicting military veterans. Currently, there are no approved therapeutics to treat sensorineural hearing loss in humans. While hearing loss affects both men and women, sexual dimorphism is documented with respect to peripheral and central auditory physiology, as well as susceptibility to age-related and noise-induced hearing loss. Physiological differences between the sexes are often hormone-driven, and an increasing body of literature demonstrates that the hormone estrogen and its related signaling pathways may in part, modulate the aforementioned differences in hearing. From a mechanistic perspective, understanding the underpinnings of the hormonal modulation of hearing may lead to the development of therapeutics for age related and noise induced hearing loss. Here the authors review a number of studies that range from human populations to animal models, which have begun to provide a framework for understanding the functional role of estrogen signaling in hearing, particularly in normal and aberrant peripheral auditory physiology.
| S-EPMC6588519 | biostudies-literature
Project description:Quiescent adult muscle stem cells (MuSCs) regenerate skeletal muscle upon injury throughout life. However, aged skeletal muscles fail to maintain stem cell quiescence, leading to declines in MuSC number and functionality. Although autophagy plays an important role in the maintenance of MuSC quiescence, how quiescent MuSCs and their autophagy levels are maintained throughout life is largely unknown. The current study reveals how GnRH, a hypothalamic hormone, maintains the quiescence of adult MuSCs by preventing the onset of senescence and how the decline of sex steroids in organismal ageing is implicated in MuSC ageing.
2019-10-05 | GSE121016 | GEO
Project description:17β-hydroxysteroid dehydrogenase (17β-HSD) type 1 is known as a critical target to block the final step of estrogen production in estrogen-dependent breast cancer. Recent confirmation of the role of dyhydroxytestosterone (DHT) in counteracting estrogen-induced cell growth prompted us to study the reductive 17β-HSD type 7 (17β-HSD7), which activates estrone while markedly inactivating DHT. The role of DHT in breast cancer cell proliferation is demonstrated by its independent suppression of cell growth in the presence of a physiological concentration of estradiol (E2). Moreover, an integral analysis of a large number of clinical samples in Oncomine datasets demonstrated the overexpression of 17β-HSD7 in breast carcinoma. Inhibition of 17β-HSD7 in breast cancer cells resulted in a lower level of E2 and a higher level of DHT, successively induced regulation of cyclinD1, p21, Bcl-2, and Bik, consequently arrested cell cycle in the G(0)/G(1) phase, and triggered apoptosis and auto-downregulation feedback of the enzyme. Such inhibition led to significant shrinkage of xenograft tumors with decreased cancer cell density and reduced 17β-HSD7 expression. Decreased plasma E2 and elevated plasma DHT levels were also found. Thus, the dual functional 17β-HSD7 is proposed as a novel target for estrogen-dependent breast cancer by regulating the balance of E2 and DHT. This demonstrates a conceptual advance on the general belief that the major role of this enzyme is in cholesterol metabolism.
| S-EPMC4664117 | biostudies-literature