High Mobility Group Box 1 Regulates Uterine Decidualization through Bone Morphogenetic Protein 2 and Plays a Role in Kruppel-Like Factor 5-Induced Stromal Differentiation
| Autor: | Zhan-Qing Yang, Zhan-Peng Yue, Bin Guo, Hai-Fan Yu, Yu-Si Wang, Kai Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Stromal cell Physiology Kruppel-Like Transcription Factors Bmp2 8-Bromo Cyclic Adenosine Monophosphate Bone Morphogenetic Protein 2 chemical and pharmacologic phenomena Biology Bone morphogenetic protein 2 lcsh:Physiology lcsh:Biochemistry Mice 03 medical and health sciences Pregnancy medicine Animals Gene silencing Decidual cells Uterine stromal cell lcsh:QD415-436 Embryo Implantation Blastocyst HMGB1 Protein RNA Small Interfering Protein kinase A Cells Cultured Cell Proliferation Hmgb1 Sulfonamides Gene knockdown lcsh:QP1-981 Uterus Decidualization Cell Differentiation Isoquinolines Klf5 Recombinant Proteins Prolactin Up-Regulation Cell biology 030104 developmental biology medicine.anatomical_structure Female RNA Interference Stromal Cells |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 48, Iss 6, Pp 2399-2408 (2018) |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | Background/Aims: High mobility group box 1 (Hmgb1) is associated with a variety of physiological processes including embryonic development, cell proliferation and differentiation, but little information is available regarding its biological role in decidualization. Methods: In situ hybridization, real-time PCR, RNA interference, gene overexpression and MTS assay were used to analyze the spatiotemporal expression of Hmgb1 in mouse uterus during the pre-implantation period, and explore its function and regulatory mechanisms during uterine decidualization. Results: Hmgb1 mRNA was obviously observed in uterine epithelium on day 2 and 3 of pregnancy, but its expression was scarcely detected on day 4 of pregnancy. With the onset of embryo implantation, abundant Hmgb1 expression was noted in the subluminal stromal cells around the implanting blastocyst at implantation sites. Meanwhile, the accumulation of Hmgb1 mRNA was visualized in the decidual cells. Hmgb1 advanced the proliferation of uterine stromal cells and induced the expression of prolactin family 8, subfamily a, member 2 (Prl8a2), a reliable differentiation marker for decidualization. In uterine stromal cells, cAMP analogue 8-Br-cAMP up-regulated the expression of Hmgb1, but the up-regulation was abrogated by protein kinase A (PKA) inhibitor H89. Silencing of Hmgb1 by specific siRNA impeded the induction of 8-Br-cAMP on Prl8a2. Further analysis evidenced that Hmgb1 was a critical mediator of Kruppel-like factor 5 (Klf5) function in stromal differentiation. Knockdown of bone morphogenetic protein 2 (Bmp2) prevented the up-regulation of Prl8a2 elicited by Hmgb1 overexpression, whereas addition of exogenous recombinant Bmp2 protein (rBmp2) reversed the repression of Hmgb1 siRNA on Prl8a2 expression. Conclusion: Hmgb1 may play an important role during mouse uterine decidualization. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|