Oh, Su­Jeong Shin, Ye Young Ahn, Ji­Su Park, Hee­Jeong Kang, Min­Jung Shin, Tae­Hoon Lee, Byung­Chul Kim, Won Kyu Oh, Jung­Min Lee, Dongjun Kim, Yun Hak Kim, Ji Min Sung, Eui­Suk Lee, Eun­Woo Jeong, Jee­Heon Lee, Byung­Joo Seo, Yoojin Kim, Hyung­Sik 2024-11-28T11:00:14Z 2024-11-28T11:00:14Z 2024-11-26 2024-12 https://pubs.kist.re.kr/handle/201004/151160 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. English Wiley-VCH Verlag TGFβ2­Driven Ferritin Degradation and Subsequent Ferroptosis Underlie Salivary Gland Dysfunction in Postmenopausal Conditions Article 10.1002/advs.202400660 1 Advanced Science, v.11, no.47 Advanced Science 11 47 Y scie scopus 001382814700001 Chemistry, Multidisciplinary Nanoscience & Nanotechnology Materials Science, Multidisciplinary Chemistry Science & Technology - Other Topics Materials Science Article TGF-BETA SERUM FERRITIN H-FERRITIN EXPRESSION RECEPTOR SEX INHIBITION XEROSTOMIA THERAPY MARKERS estrogen ferroptosis organoids salivary gland TGF beta 2 xerostomia