Estradiol promotes the development of a fibrotic phenotype and is increased in the serum of patients with systemic sclerosis

Aida-Yasuoka, Keiko; Peoples, C.E; Yasuoka, Hidekata; Hershberger, Pamela A.; Thiel, Katelynn J J.; Cauley, Jane A.; Medsger, Thomas A.; Feghali‐Bostwick, Carol

doi:10.1186/ar4140

Cited by 42 publications

(83 citation statements)

References 46 publications

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“…However, ERβ overexpression decreases JNK phosphorylation and protects intact male and female mouse hearts against fibrosis [ 16 ]. Furthermore, a recent study highlighted the fact that ERα activation in fibroblasts increased fibronectin production [ 31 ]. On the other hand, in male mice, ERβ has been demonstrated to have a beneficial role on cardiac fibrosis, at least in part by inhibiting TGF-β1 and collagen I expression in intact male and female mice (13) and OVX female mice [ 10 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

Estrogen rescues heart failure through estrogen receptor Beta activation

et al. 2018

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BackgroundRecently, we showed that exogenous treatment with estrogen (E2) rescues pre-existing advanced heart failure (HF) in mice. Since most of the biological actions of E2 are mediated through the classical estrogen receptors alpha (ERα) and/or beta (ERβ), and both these receptors are present in the heart, we examined the role of ERα and ERβ in the rescue action of E2 against HF.MethodsSevere HF was induced in male mice by transverse aortic constriction-induced pressure overload. Once the ejection fraction (EF) reached ~ 35%, mice were treated with selective agonists for ERα (PPT, 850 μg/kg/day), ERβ (DPN, 850 μg/kg/day), or E2 (30 μg/kg/day) together with an ERβ-antagonist (PHTPP, 850 μg/kg/day) for 10 days.ResultsEF of HF mice was significantly improved to 45.3 ± 2.1% with diarylpropionitrile (DPN) treatment, but not with PPT (31.1 ± 2.3%). E2 failed to rescue HF in the presence of PHTPP, as there was no significant improvement in the EF at the end of the 10-day treatment (32.5 ± 5.2%). The improvement of heart function in HF mice treated with ERβ agonist DPN was also associated with reduced cardiac fibrosis and increased cardiac angiogenesis, while the ERα agonist PPT had no significant effect on either cardiac fibrosis or angiogenesis. Furthermore, DPN improved hemodynamic parameters in HF mice, whereas PPT had no significant effect.ConclusionsE2 treatment rescues pre-existing severe HF mainly through ERβ. Rescue of HF by ERβ activation is also associated with stimulation of cardiac angiogenesis, suppression of fibrosis, and restoration of hemodynamic parameters.

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Section: Discussionmentioning

confidence: 99%

Estrogen rescues heart failure through estrogen receptor Beta activation

et al. 2018

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“…In this set of patients, we previously demonstrated that treatment with finasteride results in basal cell hyperplasia [11] , which is one hallmark of increased local estrogen levels [37] . Interestingly, higher estrogen levels can also result in increased collagen deposition [38] , suggesting that estrogen-stimulated deposition of collagen by fibroblasts, myofibroblasts, and fibrocytes through 5α-RI treatment may be contributing to remaining LUTS. However, in this study, we found no association between treatment with finasteride and changes in collagen levels.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Fibrillar Collagens and Extracellular Matrix of Glandular Benign Prostatic Hyperplasia Nodules

et al. 2014

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ObjectiveRecent studies have associated lower urinary tract symptoms (LUTS) in men with prostatic fibrosis, but a definitive link between collagen deposition and LUTS has yet to be demonstrated. The objective of this study was to evaluate ECM and collagen content within normal glandular prostate tissue and glandular BPH, and to evaluate the association of clinical parameters of LUTS with collagen content.MethodsFibrillar collagen and ECM content was assessed in normal prostate (48 patients) and glandular BPH nodules (24 patients) using Masson's trichrome stain and Picrosirius red stain. Second harmonic generation (SHG) imaging was used to evaluate collagen content. Additional BPH tissues (n = 47) were stained with Picrosirius red and the association between clinical parameters of BPH/LUTS and collagen content was assessed.ResultsECM was similar in normal prostate and BPH (p = 0.44). Total collagen content between normal prostate and glandular BPH was similar (p = 0.27), but a significant increase in thicker collagen bundles was observed in BPH (p = 0.045). Using SHG imaging, collagen content in BPH (mean intensity = 62.52; SEM = 2.74) was significantly higher than in normal prostate (51.77±3.49; p = 0.02). Total collagen content was not associated with treatment with finasteride (p = 0.47) or α-blockers (p = 0.52), pre-TURP AUA symptom index (p = 0.90), prostate-specific antigen (p = 0.86), post-void residual (PVR; p = 0.32), prostate size (p = 0.21), or post-TURP PVR (p = 0.51). Collagen content was not associated with patient age in patients with BPH, however as men aged normal prostatic tissue had a decreased proportion of thick collagen bundles.ConclusionsThe proportion of larger bundles of collagen, but not total collagen, is increased in BPH nodules, suggesting that these large fibers may play a role in BPH/LUTS. Total collagen content is independent of clinical parameters of BPH and LUTS. If fibrosis and overall ECM deposition are associated with BPH/LUTS, this relationship likely exists in regions of the prostate other than glandular hyperplasia.

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“…More recently, using primary human dermal fibroblasts, the effect of 17b-estradiol on expression of fibronectin has been evaluated with and without ICI 182, 780 (Faslodex), a steroidal estrogen antagonist (this is the first in a new class of agentan estrogen receptor downregulator) [38].…”

Section: • Rheumatoid Arthritismentioning

confidence: 99%

Estrogen’s effects in chronic autoimmune/inflammatory diseases and progression to cancer

Cutolo

Sulli

Straub

2013

Expert Review of Clinical Immunology

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Endocrine-immune system interactions are the basis for predominance of autoimmune diseases in women with differences between the fertile and the postmenopausal periods. B cell-driven diseases reach the maximum incidence rate in the reproductive years, at least in women under the effects of serum estrogens and their metabolites (endocrine synthesis). On the other hand, the prevalent peripheral synthesis of estrogens, especially in advanced ages (intracrine synthesis), through the action of aromatases, modulate the immune/inflammatory response in peripheral tissues similarly in both female and male patients (final common pathway). Interestingly, tissue injury that occurs during chronic immune/inflammatory reaction induces tissue repair and homeostatic responses including cell proliferation, growth factor production and angiogenesis that might facilitate cancer progression. The successful treatment of chronic immune/inflammatory diseases obtained by using medications initially developed for use in oncology, such as antiproliferative drugs, B-cell depleting monoclonal antibodies support the inflammation-cancer link.

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Estradiol promotes the development of a fibrotic phenotype and is increased in the serum of patients with systemic sclerosis

Cited by 42 publications

References 46 publications

Estrogen rescues heart failure through estrogen receptor Beta activation

Estrogen rescues heart failure through estrogen receptor Beta activation

Characterization of Fibrillar Collagens and Extracellular Matrix of Glandular Benign Prostatic Hyperplasia Nodules

Estrogen’s effects in chronic autoimmune/inflammatory diseases and progression to cancer

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