Levonorgestrel Ameliorates Adenomyosis via lncRNA H19/miR-17/TLR4 Pathway

N Liang, W Zhang, H Wang, Shi Wei, L Wang, Li Ma
In: Drug Design, Development and Therapy, Vol Volume 14, Pp 3449-3460 (2020) · 2020 · W4312205937
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⚙ AI-generated summary by claude@2026-06, 2026-06-11 ⓘ

Levonorgestrel treatment in adenomyosis up-regulates lncRNA H19 and down-regulates miR-17 and TLR4, leading to increased apoptosis and inhibited inflammation via this pathway.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-11 · read from full text ⓘ

This study investigated the mechanism by which levonorgestrel (LNG) ameliorates adenomyosis, focusing on the lncRNA H19/miR-17/TLR4 signaling axis. Using 71 adenomyosis patient samples versus 54 normal endometrium samples, the authors measured lncRNA H19, miR-17, and TLR4 mRNA by qPCR and TLR4 protein by Western blot, and they also evaluated LNG effects in normal endometrial stromal cells with lncRNA/miR/TLR4 suppression or overexpression vectors. They found that miR-17 and TLR4 were up-regulated and lncRNA H19 down-regulated in adenomyosis, while LNG reversed this pattern and was associated with increased apoptosis, G1 cell-cycle arrest, and reduced inflammation; a dual-luciferase reporter assay supported the lncRNA H19/miR-17/TLR4 targeting relationships. A major caveat is that functional mechanistic experiments were performed in endometrial stromal cells rather than directly in patient-derived tissues or in vivo models. This paper is centrally about adenomyosis — specifically how LNG modulates the lncRNA H19/miR-17/TLR4 pathway to ameliorate adenomyosis-related cellular changes.

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Abstract

Na Liang,1,* Wenfeng Zhang,2,* Hongjiang Wang,3 Wei Shi,4 Li Wang,2 Lijuan Ma2 1Department of Traditional Chinese Medicine, The First Affiliated Hospital of Shandong First Medical University, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan City, Shandong Province, People’s Republic of China; 2Department of Obstetrics and Gynecology, The First Affiliated Hospital of Shandong First Medical University, Shandong Provincial Qianfoshan Hospital, Jinan City, Shandong Province, People’s Republic of China; 3TCM Gynecology Department, Maternal and Child Health Hospital, Dezhou City, Shandong Province, People’s Republic of China; 4Department of Gynecology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan City, Shandong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Wang; Lijuan MaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Shandong First Medical University, Shandong Provincial Qianfoshan Hospital, No. 16766, Jingshi Road, Lixia District, Jinan City, Shandong Province, People’s Republic of ChinaTel +86-15969718268; +86-13791056924Email [email protected]; [email protected]: To explore the mechanism of levonorgestrel (LNG)-ameliorating adenomyosis through long non-coding RNA H19 (lncRNA H19)/miR-17/Toll-like receptor 4 (TLR4) pathway.Patients and Methods: A total of 71 cases of adenomyosis and 54 cases of normal endometrium were sampled. Quantitative polymerase chain reaction (qPCR) was employed to quantify lncRNA H19, miR-17, and TLR4 mRNA, while Western blot (WB) was used to quantify TLR4 protein. Effects of LNG on normal endometrial stromal cells (ESCs) were evaluated. Suppression/over-expression vectors of lncRNA H19, miR-17, and TLR4 were constructed to observe their effects on ESCs.Results: MiR-17 and TLR4 mRNA were up-regulated and lncRNA H19 was down-regulated in adenomyosis. After LNG treatment, lncRNA H19 was up-regulated while miR-17 and TLR4 were down-regulated. LNG, up-regulation of lncRNA H19, and down-regulation of miR-17 and TLR4 portend increased apoptosis, G1-arrested cells, as well as inhibited inflammation. Dual-luciferase reporter (DLR) assay conformed the targeting relation of lncRNA H19/miR-17/TLR4 pathway.Conclusion: LNG ameliorates adenomyosis via lncRNA H19/miR-17/TLR4 pathway.Keywords: adenomyosis, levonorgestrel, lncRNA H19/miR-17/TLR4 pathway
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Drug Design, Development and Therapy (Aug 2020) Levonorgestrel Ameliorates Adenomyosis via lncRNA H19/miR-17/TLR4 Pathway Abstract Na Liang,1,* Wenfeng Zhang,2,* Hongjiang Wang,3 Wei Shi,4 Li Wang,2 Lijuan Ma2 1Department of Traditional Chinese Medicine, The First Affiliated Hospital of Shandong First Medical University, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan City, Shandong Province, People’s Republic of China; 2Department of Obstetrics and Gynecology, The First Affiliated Hospital of Shandong First Medical University, Shandong Provincial Qianfoshan Hospital, Jinan City, Shandong Province, People’s Republic of China; 3TCM Gynecology Department, Maternal and Child Health Hospital, Dezhou City, Shandong Province, People’s Republic of China; 4Department of Gynecology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan City, Shandong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Wang; Lijuan MaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Shandong First Medical University, Shandong Provincial Qianfoshan Hospital, No. 16766, Jingshi Road, Lixia District, Jinan City, Shandong Province, People’s Republic of ChinaTel +86-15969718268; +86-13791056924Email [email protected]; [email protected]: To explore the mechanism of levonorgestrel (LNG)-ameliorating adenomyosis through long non-coding RNA H19 (lncRNA H19)/miR-17/Toll-like receptor 4 (TLR4) pathway.Patients and Methods: A total of 71 cases of adenomyosis and 54 cases of normal endometrium were sampled. Quantitative polymerase chain reaction (qPCR) was employed to quantify lncRNA H19, miR-17, and TLR4 mRNA, while Western blot (WB) was used to quantify TLR4 protein. Effects of LNG on normal endometrial stromal cells (ESCs) were evaluated. Suppression/over-expression vectors of lncRNA H19, miR-17, and TLR4 were constructed to observe their effects on ESCs.Results: MiR-17 and TLR4 mRNA were up-regulated and lncRNA H19 was down-regulated in adenomyosis. After LNG treatment, lncRNA H19 was up-regulated while miR-17 and TLR4 were down-regulated. LNG, up-regulation of lncRNA H19, and down-regulation of miR-17 and TLR4 portend increased apoptosis, G1-arrested cells, as well as inhibited inflammation. Dual-luciferase reporter (DLR) assay conformed the targeting relation of lncRNA H19/miR-17/TLR4 pathway.Conclusion: LNG ameliorates adenomyosis via lncRNA H19/miR-17/TLR4 pathway.Keywords: adenomyosis, levonorgestrel, lncRNA H19/miR-17/TLR4 pathway

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