Chronic oestrogen deficiency induced by ovariectomy may cause lung fibrosis through activation of the renin-angiotensin system in rats
Abstract
CONTEXT: Oestrogen deficiency is linked with pulmonary fibrosis. Additionally, it may lead to over-activation of the renin-angiotensin system (RAS), which worsens lung fibrosis. OBJECTIVE: The present study aims to investigate the role of RAS on lung fibrosis associated with oestrogen deficiency in ovariectomised rats. MATERIALS AND METHODS: -oestradiol (E2), arterial blood gases, plasma angiotensin II levels, lung tissue hydroxyproline content, and transforming growth factor beta 1 (TGF-β1) concentration, the mRNA expression of angiotensin type 1 receptor (AT1R), and angiotensin-converting enzyme (ACE1) were evaluated. Moreover, lung tissues were examined by histopathology and immunohistochemistry. RESULTS: Hydroxyproline content, TGF-β1 concentration, plasma angiotensin II, the relative mRNA expression of ACE1, and AT1R is found to increase in ovariectomised rats. The mentioned changes can be largely rescued by administration of RAS blockers. CONCLUSION: Oestrogen deficiency activates RAS, which consequently increases the expression of pro-fibrotic factors and stimulates the fibrotic cascade causing lung fibrosis.
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Estrogen activates Ang II binding to AT2R.
“Estrogen inhibits Ang II binding to AT1R, but activates Ang II binding to AT2R [8, 29, 34].”
Estrogen inhibits ACE expression and activity in rodent models.
“Researchers have reported that both ACE expression and activity are inhibited by estrogen in rodent models [26-29].”
Estrogen inhibits Ang II binding to AT1R.
“Estrogen inhibits Ang II binding to AT1R, but activates Ang II binding to AT2R [8, 29, 34].”
Cites
Chronic Activation of the Renin-Angiotensin System Induces Lung Fibrosis
Wang, J., Chen, L., Chen, B., Meliton, A., Liu, S. Q., Shi, Y., Liu, T., Deb, D. K., Solway, J., & Chun Li, Y. (2015) · Scientific Reports · doi:10.1038/srep15561 · Cited by 70 · see citing works
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Modulation of blood pressure by estrogen: A modeling analysis
Layton, A. T. (2026) · Mathematical Biosciences · doi:10.1016/j.mbs.2025.109610 · Cited by 1 · see citing works
Stadt, M. M., & Layton, A. T. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.01.651663
“Estrogen inhibits Ang II binding to AT1R, but activates Ang II binding to AT2R [8, 29, 34].”
- Authors
- Hussien, N. I., El-kerdasy, H. I., Sorour, S. M., & Shoman, A. A.
- Affiliations
- Benha University (EG)
- Department of Anatomy, Faculty of Medicine, Benha University
- Corresponding author
- Hussien, Noha I.
- Venue
- Archives of Physiology and Biochemistry
- Publisher
- Informa UK Limited
- Published
- 2019-10-12
- Volume
- 128
- Issue
- 2
- Pages
- 290-299
- ISSN
- 0778-3124 (ISSN-L)
- 1381-3455
- 1744-4160
- OpenAlex
- W2979648015
- Cited by
- 11
- References
- 1
- Citations by year
- 2026: 2 · 2025: 4 · 2022: 1 · 2021: 1 · 2020: 3
- FWCI
- 0.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Physiology and Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
- Keywords
- estrogen deficiency, ovariectomy, pulmonary fibrosis, renin-angiotensin system, angiotensin II, angiotensin II type 1 receptor, angiotensin-converting enzyme, TGF-β1, hydroxyproline, postmenopausal women
- MeSH terms
- Animals, Estrogens, Female, Humans, Ovariectomy, Pulmonary Fibrosis, Renin-Angiotensin System, Receptor, Angiotensin, Type 1, Rats
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