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Increased Expression of Fibroblast Activation Protein is Associated with Autophagy Dysregulation and Oxidative Stress in Obese Women with Uterine Fibroids

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Abstract

Uterine fibroids (UF) represent an immense health burden throughout the world. Obesity is considered one of the risk factors for UF development; however, the underlying mechanisms remain largely unexplored. We investigated the effect of obesity on fibroblast activation and its association with inflammation, autophagy dysfunction, and oxidative stress in UF patients. Thirty-five pre-menopausal UF patients were included in this study and classified into non-obese group (BM1 ≤ 30 kg/m2, n = 15) and obese group (BMI > 30 kg/m2, n = 20). Tissue samples were collected from fibroids and adjacent normal myometrium. Our results showed increased expression of fibroblast activation protein (FAP) together with markers of autophagy, inflammation, and oxidative stress in UF patients, which were all more markedly upregulated in obese compared to non-obese patients. In addition, BMI was significantly positive correlated with FAP and autophagy markers. In conclusion, the results of the present study suggest that obesity-associated autophagy dysregulation together with increased FAP expression may increase the risk of UFs in obese women.

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Funding

This research received a grant from the Assiut Medical School Grant Office. Grant no 2018-02-27-006-R1.

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Authors and Affiliations

  1. Department of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt

    Nashwa Maghraby, Amira M. El Noweihi, Nagla T. El-Melegy & Eman Radwan

  2. Department of Histology, Faculty of Medicine, Assiut University, Assiut, Egypt

    Nashwa A. M. Mostafa

  3. Department of Obstetrics and Gynecology, Faculty of Medicine, Assiut University, Assiut, Egypt

    Ahmed M. Abbas

  4. Department of Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt

    Heba E. M. El-Deek

  5. Department of Biochemistry, Sphinx University, New Assiut City, Assiut 10, Egypt

    Eman Radwan

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  1. Nashwa Maghraby
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  2. Amira M. El Noweihi
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  3. Nagla T. El-Melegy
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  4. Nashwa A. M. Mostafa
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Contributions

Eman Radwan and Nashwa Maghraby: conceptualization, methodology, software, data curation, investigation, formal analysis, writing, visualization, and supervision; Nashwa A.M. Mostafa: methodology, investigation, formal analysis, visualization; Heba E.M El-Deek: methodology, investigation, formal analysis; Amira El-Noweihi and Nagla T. El-Melegy: conceptualization, visualization writing–reviewing, and editing; Ahmed M. Abbas: data curation, investigation, and formal analysis.

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Correspondence to Eman Radwan.

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All study procedures were approved by the Medical Ethics Committee, Faculty of Medicine, and Assiut University (IRB no: 17200173).

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Maghraby, N., El Noweihi, A.M., El-Melegy, N.T. et al. Increased Expression of Fibroblast Activation Protein is Associated with Autophagy Dysregulation and Oxidative Stress in Obese Women with Uterine Fibroids. Reprod. Sci. 29, 448–459 (2022). https://doi.org/10.1007/s43032-021-00810-0

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