Indukálható bone morphogenetic protein 7 (BMP-7) termelő fogbél eredetű őssejtvonal létrehozása és vizsgálata

Morphogenetic Protein

A fogak pulpájából kinyerhető fogbél eredetű őssejtek olyan multipotens sejtek, amelyek többféle kötőszöveti sejttípussáképesek differenciálódni. Egyszerű izolálásuk és sejttenyészetekben történő fenntarthatóságuk többek között kívánatossáteszi szövetregenerációs folyamatokban donorként történő felhasználásukat is. A BMP-7 fehérje a TGF-β szupercsaládtagja, növekedési faktor, amely fontos szerepet játszik az osteoblast irányú differenciálódás indukciójában,OP-1 néven rutinszerűen alkalmazzák gerincműtéteknél és hosszú csöves csontok törésének rögzítése során. Jelenmunkánkban lentivirális géntranszferrel egy tetracyclinnel indukálható (Tet-ON) BMP-7 termelésre képes fogbél eredetűőssejtvonalat hoztunk létre, amelyben az expresszió mértéke a hozzáadott indukáló ágens (doxycyclin) mennyiségévelszabályozható, annak megvonásával pedig megszüntethető. Reményeink szerint ez az indukálható BMP-7 expresszióelősegítheti, illetve felgyorsíthatja a környező sejtek csont irányú differenciálódását in vitro és in vivo egyaránt.

Bone morphogenetic protein-7 prevented epithelial-mesenchymal transition in RLE-6TN cells

Toxicology Research ◽

10.1039/c5tx00471c ◽

2016 ◽

Vol 5 (3) ◽

pp. 931-937 ◽

Cited By ~ 2

Author(s):

Yan Wang ◽

Di Liang ◽

Zhonghui Zhu ◽

Xiaoli Li ◽

Guoliang An ◽

...

Keyword(s):

Transcription Factor ◽

Signaling Pathway ◽

P38 Mapk ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Morphogenetic Protein

Silica induced EMT and decreased the expression of BMP-7 in vivo and in vitro, while exogenous BMP-7 promoted MET and inhibited silica-induced EMT associated with inhibition of the p38 MAPK/transcription factor (TF) signaling pathway in RLE-6TN cells.

Identification of bone morphogenetic protein 7 (BMP7) as an instructive factor for human epidermal Langerhans cell differentiation

Journal of Experimental Medicine ◽

10.1084/jem.20130275 ◽

2013 ◽

Vol 210 (12) ◽

pp. 2597-2610 ◽

Cited By ~ 68

Author(s):

Nighat Yasmin ◽

Thomas Bauer ◽

Madhura Modak ◽

Karin Wagner ◽

Christopher Schuster ◽

...

Keyword(s):

Prenatal Development ◽

Langerhans Cell ◽

Type I ◽

Blood Monocytes ◽

Morphogenetic Protein ◽

Tgf Β1

Human Langerhans cell (LC) precursors populate the epidermis early during prenatal development and thereafter undergo massive proliferation. The prototypic antiproliferative cytokine TGF-β1 is required for LC differentiation from human CD34+ hematopoietic progenitor cells and blood monocytes in vitro. Similarly, TGF-β1 deficiency results in LC loss in vivo. However, immunohistology studies revealed that human LC niches in early prenatal epidermis and adult basal (germinal) keratinocyte layers lack detectable TGF-β1. Here we demonstrated that these LC niches express high levels of bone morphogenetic protein 7 (BMP7) and that Bmp7-deficient mice exhibit substantially diminished LC numbers, with the remaining cells appearing less dendritic. BMP7 induces LC differentiation and proliferation by activating the BMP type-I receptor ALK3 in the absence of canonical TGF-β1–ALK5 signaling. Conversely, TGF-β1–induced in vitro LC differentiation is mediated via ALK3; however, co-induction of ALK5 diminished TGF-β1–driven LC generation. Therefore, selective ALK3 signaling by BMP7 promotes high LC yields. Within epidermis, BMP7 shows an inverse expression pattern relative to TGF-β1, the latter induced in suprabasal layers and up-regulated in outer layers. We observed that TGF-β1 inhibits microbial activation of BMP7-generated LCs. Therefore, TGF-β1 in suprabasal/outer epidermal layers might inhibit LC activation, resulting in LC network maintenance.

Bone morphogenetic protein 7 attenuates epithelial–mesenchymal transition induced by silica

Human & Experimental Toxicology ◽

10.1177/0960327115577550 ◽

2015 ◽

Vol 35 (1) ◽

pp. 69-77 ◽

Cited By ~ 15

Author(s):

G Yang ◽

Z Zhu ◽

Y Wang ◽

A Gao ◽

P Niu ◽

...

Keyword(s):

Pulmonary Fibrosis ◽

Epithelial Mesenchymal Transition ◽

A549 Cells ◽

Mesenchymal Transition ◽

Morphogenetic Protein ◽

Epithelial Marker

The epithelial–mesenchymal transition (EMT) is a critical process in the pulmonary fibrosis. It has been reported that bone morphogenetic protein 7 (BMP-7) was able to reverse EMT in proximal tubular cells. Therefore, we test the hypothesis that EMT contributes to silica-induced pulmonary fibrosis and BMP-7 inhibits EMT in silica-induced pulmonary fibrosis. Progressive silica-induced pulmonary fibrosis in the rat was used as a model of silicosis. Epithelial and mesenchymal markers were measured from rat fibrotic lungs. Then the effects of BMP-7 on the EMT were further confirmed in A549 cells. There are increases of vimentin as a mesenchymal marker and decreases of E-cadherin as an epithelial marker in the silica-exposed rat lungs, which is in agreement with the A549 cells data. However, BMP-7 treatment significantly reduced expression of vimentin in the rat pulmonary fibrosis model and in A549 cells. In conclusion, EMT contributes to silica-induced pulmonary fibrosis. Meanwhile, the treatment of BMP-7 can inhibit silica-induced EMT in vitro and in vivo.