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bone morphogenetic protein-6 suppresses TGF-β_(2)-induced epithelial-mesenchymal transition in retinal pigment epithelium

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International Journal of Ophthalmology(English edition) 2024年第4期17卷 646-652页

作者： Xuan Liu Ming Liu Meng Ji Bo Ma Yu-Cen Hou Xin-Yue Yao Qiao-Chu Cheng Li Chen Department of Ophthalmology the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Department of Ophthalmology Xi’an No.1 HospitalXi’an 710000Shaanxi ProvinceChina Shaanxi Institute of Ophthalmology Xi’an 710000Shaanxi ProvinceChina Department of Ophthalmology Ankang Hospital of Traditional Chinese MedicineAnkang 725000Shaanxi ProvinceChina

AIM:To evaluate the effect of bone morphogenetic protein-6(BMP-6)on transforming growth factor(TGF)-β_(2)-induced epithelial-mesenchymal transition(EMT)in retinal pigment epithelium(RPE).METHODS:Adult retinal pigment epithelial cell line(ARPE-19)were randomly divided into control,TGF-β_(2)(5μg/L),and BMP-6 small interfering RNA(siRNA)*** cell morphology was observed by microscopy,and the cell migration ability were detected by Transwell *** EMT-related indexes and BMP-6 protein levels were detected by Western ***,a BMP-6 overexpression plasmid was constructed and RPE cells were divided into the control group,TGF-β_(2)+empty plasmid group,BMP-6 overexpression group,and TGF-β_(2)+BMP-6 overexpression *** EMT-related indexes and extracellular regulated protein kinases(ERK)protein levels were ***:Compared with the control group,the migration of RPE cells in the TGF-β_(2) group was significantly ***-β_(2) increased the protein expression levels ofα-smooth muscle actin(α-SMA),fibronectin and vimentin but significantly decreased the protein levels of E-cadherin and BMP-6(P6 siRNA group was also significantly ***-6 siRNA increased the protein expression levels ofα-SMA,fibronectin and vimentin but significantly decreased the protein expression levels of E-cadherin(P6 inhibited the migration of RPE cells induced by TGF-β_(2) and prevented TGF-β_(2) from affecting EMT-related biomarkers(P6 prevents the EMT in RPE cells induced by TGF-β_(2),which may provide a theoretical basis for the prevention and treatment of proliferative vitreoretinopathy.

关键词： bone morphogenetic protein-6 epithelialmesenchymal transition transforming growth factor-β_(2) retinal pigment epithelial cells cell migration

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Chondrogenesis of periodontal ligament stem cells by transforming growth factor-β3 and bone morphogenetic protein-6 in a normal healthy impacted third molar

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International Journal of Oral Science 2013年第1期5卷 7-13页

作者： Sunyoung Choi Tae-Jun Cho Soon-Keun Kwon Gene Lee Jaejin Cho Laboratory of Developmental Biology and Stem Cell Differentiation/Transplantation Department of Dental Regenerative BiotechnologySchool of DentistrySeoul National University Dental Research Institute School of DentistrySeoul National University Laboratory of Molecular Genetics School of DentistrySeoul National University

The periodontal ligament-derived mesenchymal stem cell is regarded as a source of adult stem cells due to its ***, the proof of chondrogenic potential of the cells is ***,we investigated the chondrogenic differentiation capacity of periodontal ligament derived mesenchymal stem cells induced by transforming growth factor(TGF)-p3 and bone morphogenetic protein(BMP)-*** isolation of periodontal ligament stem cells(PDLSCs) from human periodontal ligament,the cells were cultured in Dulbecco’s modified Eagle’s medium(DMEM) with 20%fetal bovine serum(FBS).A mechanical force initiated chondrogenic differentiation of the *** chondrogenic differentiation,10μg·LTGF-β3 or 100μg·LBMP-6 and the combination treating group for synergistic effect of the growth *** analyzed the PDLSCs by fluorescence-activated cell sorting and chondrogenesis were evaluated by glycosaminoglycans assay,histology,immunohistochemistry and genetic *** showed mesenchymal stem cell properties proved by FACS *** contents were increased 217%by TGF-β3 and 220%by BMP-6. The synergetic effect of TGF-β3 and BMP-6 were shown up to 281%compared to *** combination treatment increased Sox9, aggrecan and collagen II expression compared with not only controls,but also TGF-P3 or BMP-6 single treatment *** histological analysis also indicated the chondrogenic differentiation of PDLSCs in our *** results of the present study demonstrate the potential of the dental stem cell as a valuable cell source for chondrogenesis,which may be applicable for regeneration of cartilage and bone fracture in the field of cell therapy.

关键词： bone morphogenetic protein-6 chondrogenesis growth factor periodental ligament cell stem cell transforming growth factor-β3

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Activation of bone morphogenetic protein-6 gene transcription in MCF-7 cells by estrogen

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Chinese Medical Journal 2005年第19期118卷 1629-1636页

作者： ZHANG Ming YAN Ji-dong ZHANG Lei WANG Qing Lü Shu-jun ZHANG Jie ZHU Tian-hui Laboratory of Molecular Medicines Medical College Nankai University Tianjin 300071 China

Background bone morphogenetic protein-6 （BMP-6） is closely correlated with tumor differentiation and skeletal metastasis. Estrogen is considered as a stimulant for the initiation and promotion of breast cancer. Previous studies demonstrated that 17β-estadiol （E2） can selectively increase the expression of BMP-6. This experiment is designed to detect the molecular mechanism of estrogen activating BMP-6 gene transcription in human estrogen receptor positive （ER ^＋） breast cancer cell line MCF-7. Methods After the treatment of MCF-7 cells with E2 at different concentrations （ 10^-11 mol/L, 10.9 mol/L, 10.7 mol/L）, the BMP-6 expression level was examined through real-time polymerase chain reaction. Through restriction enzyme digestion, human BMP-6 1.2 kb long promoter, BMP-6 0. 7 kb long promoter was cloned into pGL-3 basic vector; after the treatment with 10^-7 mol/L E2, luciferase activities of the two promoters were detected. Site-directed mutagenesis was performed to obtain the mutant forms of estrogen response element half- site （ 1/2 ERE） element and Spl sites in the BMP-6 promoter, the activities of these mutant form promoters were detected following the methods mentioned above. Chromatin immunoprecipitation （CHIP） assay was also used to confirm the binding of estrogen receptor a （ERα） on BMP-6 promoter in the presence of E2. Results E2 dose dependently increased BMP-6 mRNA expression in human ER ^＋ breast cancer cell line MCF-7. At a dose of 10^-7 mol/L E2, human BMP-6 1.2 kb promoter activity was increased by 90% compared with the control group treated with ethanol （P 〈 0. 05 ）. Both the 1/2 ERE response element mutant form and the Spl site mutant form of the BMP-6 promoter abolished the activation of the BMP-6 promoter＇ s response to E2. Through ChIP assay, the binding of ERot on 1/2 ERE response element in BMP-6 promoter was further validated. Conclusion Estrogen induces BMP-6 expression in human ER^＋ breast cancer cell line MCF-7 receptor ERα binding on 1/2

关键词： bone morphogenetic protein-6 estrogen chromatin immunoprecipitation site-directed mutagenesis

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