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journal article·2024-12Open access

TGFβ2‐Driven Ferritin Degradation and Subsequent Ferroptosis Underlie Salivary Gland Dysfunction in Postmenopausal Conditions

Su‐Jeong Oh, Ye Young Shin, Ji‐Su Ahn, Hee‐Jeong Park, Min‐Jung Kang, Tae‐Hoon Shin, Byung‐Chul Lee, Won Kyu Kim, Jung‐Min Oh, Dongjun Lee, Yun Hak Kim, Ji Min Kim, Eui‐Suk Sung, Eun‐Woo Lee, Jee‐Heon Jeong, Byung‐Joo Lee, Yoojin Seo, Hyung‐Sik Kim

Advanced Science· Volume 11· Issue 47
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Source abstract

Abstract

Abstract Despite the high incidence of dry mouth in postmenopausal women, its underlying mechanisms and therapeutic interventions remain underexplored. Using ovariectomized (OVX) mouse models, here this study identifies ferroptosis, an iron‐dependent regulated cell death, as a central mechanism driving postmenopausal salivary gland (SG) dysfunction. In the OVX‐SGs, TGFβ signaling pathway is enhanced with the aberrant TGFβ2 expression in SG mesenchymal cells. Intriguingly, TGFβ2 treatment reduces iron‐storing ferritin levels, leading to lipid peroxidation and ferroptotic death in SG epithelial organoids (SGOs). Mechanistically, TGFβ2 promotes the autophagy‐mediated ferritin degradation, so‐called ferritinophagy. A notable overexpression of the type III TGFβ receptor (TβRIII) is found in the OVX‐SGs and TGFβ2‐treated SGOs, while the silencing of TβRIII mitigates the ferroptosis‐mediated deleterious effects of TGFβ2 on SGOs. Finally, administration of ferroptosis inhibitor, Liproxstatin‐1 (Lip‐1), improves saliva secretion in OVX mice. Present findings collectively suggest a link between TGFβ signaling, ferroptosis, and SG injury, offering new therapeutic avenues for postmenopausal xerostomia.
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Research context

OpenAlex topics: Cancer-related molecular mechanisms research · Salivary Gland Disorders and Functions · Growth Hormone and Insulin-like Growth Factors

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry Pusan National University Yangsan 50612 Republic of Korea

Department of Life Science in Dentistry School of Dentistry Pusan National University Yangsan 50612 Republic of Korea

Education and Research Team for Life Science on Dentistry Pusan National University Yangsan 50612 Republic of Korea

Stem Cell and Regenerative Bioengineering Institute Global R&D Center Kangstem Biotech Co. Ltd. Seoul 08590 Republic of Korea

Department of Laboratory Animal Medicine College of Veterinary Medicine and Veterinary Medical Research Institute Jeju National University Jeju‐si 63243 Republic of Korea

Department of Biological Sciences Sookmyung Women's University Seoul 04310 Republic of Korea

Research Institute of Women’s Health Sookmyung Women’s University Seoul 04310 Republic of Korea

Natural Product Research Center Korea Institute of Science andTechnology (KIST) Gangneung 25451 Republic of Korea

Department of Convergence Medicine Yonsei University Wonju College of Medicine Wonju 26426 Republic of Korea

Division of Natural Products Applied Science University of Science and Technology (UST) Daejeon 34113 Republic of Korea

Department of Convergence Medicine Pusan National University School of Medicine Yangsan 50612 Republic of Korea

Department of Anatomy Pusan National University School of Medicine Yangsan 50612 Republic of Korea

Department of Otorhinolaryngology‐Head and Neck Surgery Pusan National University School of Medicine and Biomedical Research Institute Pusan National University Hospital Busan 49241 Republic of Korea

Department of Otorhinolaryngology‐Head and Neck Surgery Biomedical Research Institute Pusan National University School of Medicine Yangsan Pusan National University Hospital Yangsan 50612 Republic of Korea

Metabolic Regulation Research Center Korea Research Institute of Bioscience and Biotechnology (KRIBB) Daejeon 34141 Republic of Korea

School of Pharmacy Sungkyunkwan University Suwon 16419 Republic of Korea

Department of Precision Medicine School of Medicine Sungkyunkwan University Suwon 16419 Republic of Korea

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