scholarly journals BMP4/Smad Signaling Pathway Induces the Differentiation of Mouse Spermatogonial Stem Cells via Upregulation of Sohlh2

2014 ◽  
Vol 297 (4) ◽  
pp. 749-757 ◽  
Author(s):  
Yi Li ◽  
Yuecun Zhang ◽  
Xiaoli Zhang ◽  
Jinhao Sun ◽  
Jing Hao
Keyword(s):  
Stem Cells ◽  
Signaling Pathway ◽  
Spermatogonial Stem Cells ◽  
Smad Signaling ◽  
Smad Signaling Pathway

U0126 promotes osteogenesis of rat bone-marrow-derived mesenchymal stem cells by activating BMP/Smad signaling pathway

2014 ◽  
Vol 359 (2) ◽  
pp. 537-545 ◽  
Author(s):  
Liangliang Xu ◽  
Yang Liu ◽  
Yonghui Hou ◽  
Kuixing Wang ◽  
Yinmei Wong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathway ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
Rat Bone

Smad7 promotes self-renewal of hematopoietic stem cells

Blood ◽  
2006 ◽  
Vol 108 (13) ◽  
pp. 4246-4254 ◽  
Author(s):  
Ulrika Blank ◽  
Goran Karlsson ◽  
Jennifer L. Moody ◽  
Taiju Utsugisawa ◽  
Mattias Magnusson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Smad Pathway ◽  
Smad Signaling ◽  
Smad Signaling Pathway

Abstract The Smad-signaling pathway downstream of the transforming growth factor–β superfamily of ligands is an evolutionarily conserved signaling circuitry with critical functions in a wide variety of biologic processes. To investigate the role of this pathway in the regulation of hematopoietic stem cells (HSCs), we have blocked Smad signaling by retroviral gene transfer of the inhibitory Smad7 to murine HSCs. We report here that the self-renewal capacity of HSCs is promoted in vivo upon blocking of the entire Smad pathway, as shown by both primary and secondary bone marrow (BM) transplantations. Importantly, HSCs overexpressing Smad7 have an unperturbed differentiation capacity as evidenced by normal contribution to both lymphoid and myeloid cell lineages, suggesting that the Smad pathway regulates self-renewal independently of differentiation. Moreover, phosphorylation of Smads was inhibited in response to ligand stimulation in BM cells, thus verifying impairment of the Smad-signaling cascade in Smad7-overexpressing cells. Taken together, these data reveal an important and previously unappreciated role for the Smad-signaling pathway in the regulation of self-renewal of HSCs in vivo.

scholarly journals NANOG regulates the proliferation of PCSCs via the TGF-β1/SMAD pathway

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 841-849
Author(s):  
Changming Liu ◽  
Mingxiong Sheng ◽  
Liheng Lin ◽  
Huizhang Li ◽  
Shanming Guo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Signaling Pathway ◽  
Biological Behavior ◽  
Castration Resistance ◽  
Smad Signaling ◽  
Prostate Cancer Stem Cells ◽  
Smad Signaling Pathway ◽  
Tgf Β1

AbstractPurposeIn prostate cancer, castration resistance is a factor that frequently leads to death in individuals with this disease. Recent studies have suggested that prostate cancer stem cells (PCSCs) are pivotal regulators in the establishment of castration resistance. The nanog homeobox (NANOG) and the transforming growth factor (TGF)-β1/drosophila mothers against decapentaplegic protein (SMAD) signaling pathways are involved in several cancer stem cells but are not involved in PCSCs. The purpose of this study is to investigate the effect of NANOG on the proliferation of PCSCs regulated by the TGF-β1/SMAD signaling pathway.MethodsIn this study, we used flow cytometry to isolate CD44+/CD133+/NANOG+ PCSCs from DU145 prostate cancer cells. Then we used short hairpin RNA to silence NANOG and observed the biological behavior and the TGF-β1/SMAD signal of PCSCs.ResultsNANOG decreased PCSC proliferation, increased apoptosis, and blocked cell cycling at G0/G1. Furthermore, reduction in the TGF-β1, p15, and p-SMAD2 expression was observed.ConclusionThese findings suggest that NANOG positively regulates the growth of PCSCs through the TGF-β1/SMAD signaling pathway.

scholarly journals Inhibitory effect of the TSG-6 on the BMP-4/Smad signaling pathway and odonto/osteogenic differentiation of dental pulp stem cells

2020 ◽  
Author(s):  
Ying Wang ◽  
Shuai Yuan ◽  
Jingjing Sun ◽  
Yuping Gong ◽  
Sirui Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Signaling Pathway ◽  
Nude Mice ◽  
Dental Pulp ◽  
Dental Pulp Stem Cells ◽  
Smad Signaling ◽  
Osteogenic Markers ◽  
Tnf Α ◽  
Smad Signaling Pathway

AbstractThis study aimed to observe the molecular mechanism underlying the effect of tumor necrosis factor–inducible protein 6 (TSG-6) on the bone morphogenetic protein-4 (BMP-4)/drosophila mothers against decapentaplegic protein(Smad) signaling pathway and mineralization of dental pulp stem cells (DPSCs) in inflammatory environment. Normal and TSG-6 gene–modified DPSCs were cultured in a mineralization-inducing fluid containing 0 and 50 ng/mL TNF-α separately. The real-time polymerase chain reaction was used to measure the expression of TSG-6 and odonto/osteogenic differentiation makers at the mRNA level. Western blot analysis and cellular immunofluorescence were used to observe the odonto/osteogenic differentiation of DPSCs and the variation of BMP-4/Smad signaling pathway at the protein level. Moreover, normal and modified DPSCs combined with hydrogel were used for subcutaneous implantation in nude mice. The expression of odonto/osteogenic markers and BMP-4/Smad-related proteins was lower in Ad-TSG-6 DPSCs than in normal DPSCs after mineralization induction, and was higher in TSG-6-RNAi DPSCs than in normal DPSCs after culturing with mineralization-inducing fluid containing 50 ng/mL TNF-α. The subcutaneous transplantation of normal and modified DPSCs combined with hydrogel in nude mice demonstrated that normal DPSCs were formed in the tissue containing collagen. The tissue formed by Ad-TSG-6 DPSCs was highly variable, and the cells were very dense. The expression of odonto/osteogenic markers of Ad-TSG-6 DPSCs were lower in Ad-TSG-6 DPSCs than in normal DPSCs. We can know that TNF-α regulates the expression of TSG-6, thereby inhibiting the BMP-4/Smad signaling pathway and the odonto/osteogenic differentiation ability of DPSCs.

scholarly journals ALK5 i II Accelerates Induction of Adipose-Derived Stem Cells toward Schwann Cells through a Non-Smad Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Seiji Sawai ◽  
Tsunao Kishida ◽  
Shin-ichiro Kotani ◽  
Shinji Tsuchida ◽  
Ryo Oda ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathway ◽  
Schwann Cells ◽  
Transforming Growth Factor ◽  
Specific Inhibitor ◽  
Stem Cell Markers ◽  
Adipose Derived Stem Cells ◽  
Smad Signaling ◽  
Smad Signaling Pathway

Schwann cells (SCs) are likely to be a vital component of cell-based therapies for nerve regeneration. There are various methods for inducing SC-like cells (SCLCs) from adipose-derived stem cells (ADSCs), but their phenotypic and functional characteristics remain unsatisfactory. Here, we report a novel efficient procedure to induce SCLCs by culturing ADSCs with ALK5 inhibitor (ALK5 i) II, a specific inhibitor of activin-like kinase 5 (ALK5) (transforming growth factor-β receptor 1 (TGFβR1)) that is also known as Repsox. The resultant cells that we named “modified SCLCs (mSCLCs)” expressed SC-specific genes more strongly than conventional SCLCs (cSCLCs) and displayed a neurosupportive capacity in vitro, similarly to genuine SCs. Regarding the mechanism of the mSCLC induction by ALK5 i II, knockdown of Smad2 and Smad3, key proteins in the TGFβ/Smad signaling pathway, did not induce SC markers. Meanwhile, expression of multipotent stem cell markers such as Sex-determining region Y- (SRY-) box 2 (Sox2) was upregulated during induction. These findings imply that ALK5 i II exerts its effect via the non-Smad pathway and following upregulation of undifferentiated cell-related genes such as Sox2. The procedure described here results in highly efficient induction of ADSCs into transgene-free and highly functional SCLCs. This approach might be applicable to regeneration therapy for peripheral nerve injury.

scholarly journals Epigallocatechin-3-Gallate Promotes Osteo-/Odontogenic Differentiation of Stem Cells from the Apical Papilla through Activating the BMP–Smad Signaling Pathway

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1580
Author(s):  
Zeni Liu ◽  
Yuxiu Lin ◽  
Xiaolin Fang ◽  
Jingwen Yang ◽  
Zhi Chen
Keyword(s):  
Stem Cells ◽  
Alkaline Phosphatase ◽  
Signaling Pathway ◽  
Matrix Protein ◽  
Type I ◽  
Alizarin Red ◽  
Smad Signaling ◽  
Odontogenic Differentiation ◽  
Smad Signaling Pathway ◽  
Apical Papilla

Stem cells from apical papilla (SCAPs) are desirable sources of dentin regeneration. Epigallocatechin-3-gallate (EGCG), a natural component of green tea, shows potential in promoting the osteogenic differentiation of bone mesenchymal stem cells. However, whether EGCG regulates the odontogenic differentiation of SCAPs and how this occurs remain unknown. SCAPs from immature human third molars (16–20 years, n = 5) were treated with a medium containing different concentrations of EGCG or bone morphogenic protein 2 (BMP2), with or without LDN193189 (an inhibitor of the canonical BMP pathway). Cell proliferation and migration were analyzed using a CCK-8 assay and wound-healing assay, respectively. Osteo-/odontogenic differentiation was evaluated via alkaline phosphatase staining, alizarin red S staining, and the expression of osteo-/odontogenic markers using qPCR and Western blotting. We found that EGCG (1 or 10 μM) promoted the proliferation of SCAPs, increased alkaline phosphatase activity and mineral deposition, and upregulated the expression of osteo-/odontogenic markers including dentin sialophosphoprotein (Dspp), dentin matrix protein-1 (Dmp-1), bone sialoprotein (Bsp), and Type I collagen (Col1), along with the elevated expression of BMP2 and phosphorylation level of Smad1/5/9 (p < 0.01). EGCG at concentrations below 10 μM had no significant influence on cell migration. Moreover, EGCG-induced osteo-/odontogenic differentiation was significantly attenuated via LDN193189 treatment (p < 0.01). Furthermore, EGCG showed the ability to promote mineralization comparable with that of recombinant BMP2. Our study demonstrated that EGCG promotes the osteo-/odontogenic differentiation of SCAPs through the BMP–Smad signaling pathway.

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