Introduction to Oral and Craniofacial Tissue Engineering
Vincenzo Guarino, Marco Antonio Alvarez-Pérez in Current Advances in Oral and Craniofacial Tissue Engineering, 2020
Bone Morphogenetic Proteins (BMP) are a group of proteins involved in multiple development processes which include skeletal formation, embryogenesis, hematopoiesis and neurogenesis. These proteins belong to the Transforming Growth Factor Beta superfamily, and over 20 members have been characterized. Four groups are formed to classify these proteins based on its amino acid sequence similarity: BMP2/4, BMP5/6/7/8a/8b, BMP9/10, and BMP12/13/14. These proteins are synthetized as a large precursor from 400–500 aa, which has three main domains, N-terminal secretion signal, a prodomain and a C-terminal region that constitutes the mature protein. Most of BMPs have seven cysteine residues in the C-terminal region, which are involved in its self-assembly and is known as a cysteine knot. BMPs functioning depends on the structural arrangement as homo- or heterodimers, which in turn are associated with specific membrane serine/threonine receptors denoted as type I and type II to trigger two main signal pathways: Smad (mothers against decapentaplegic) dependent pathway and Mitogen-Activated Protein Kinase (MAPK) pathway. This BMPs-MAPK signal pathway has shown its potential as an inductor of mesenchymal stem cells differentiation into osteoblasts, this extracellular signal is transduced inside the nucleus via the activation of ERK1/2, p38, INK 1/2/3 cascades which activate specific transcriptional factors (RUNX2, DLX5, and Osterix) related with the osteoblastic commitment and initiate the production of bone matrix proteins, leading to bone morphogenesis (Ripamonti 2019; Anusuya et al. 2016).
Transforming Growth Factor-β: A Cytokine Paradigm
Thomas F. Kresina in Immune Modulating Agents, 2020
Unraveling the complex mechanisms whereby immune cells modulate the host response to injury, inflammation, and/or infection has revealed the involvement of small protein molecules, released by activated cells, which function as chemical messengers. These messenger molecules, called cytokines and/or growth factors, provide an essential means of communication between cells within the body and mediate cellular, physiological, and immunological processes that are critical to the host response to injury or antigenic insult. The balance of these activities is critical not only to maintain normal homeostasis but also to allow for a controlled biological response that is not injurious to the host. Dysregulation of cytokine expression is often observed in disease and may provide a basis for therapeutic intervention in certain situations. Transforming growth factor-beta (TGF-β) is such a cytokine/growth factor that has a wide range of biological activities and has been implicated in immune and inflammatory disorders [1]. Manipulation of TGF-β expression in these disorders may provide insight into its mechanism of action as well as its therapeutic usefulness.
Airway Wall Remodelling in the Pathogenesis of Asthma: Cytokine Expression in the Airways
Alastair G. Stewart in AIRWAY WALL REMODELLING in ASTHMA, 2020
A number of other cytokines exist which are likely to influence airway fibrotic responses. Transforming growth factor-beta (TGFβ) denotes a family of three closely related molecules denoted TGFβ1, TGFβ2, and TGFβ3. TGFβ1 is an extremely potent modulator of the ECM. It enhances the synthesis by fibroblasts of very many components of the ECM, including collagen types I and III,155–158 fibronectin,155,157–160 tenascin,161 and proteoglycans.162 It also increases expression of cell surface receptors for several of these molecules,160,163 so as to facilitate cell–matrix interactions. In addition, TGFβ decreases the synthesis of several enzymes which are involved in the degradation of ECM components, such as plasminogen activator,164 type I collagenase, and metalloproteinases,165 and conversely increases the synthesis of molecules which inhibit these enzymes, such as type I plasminogen activator inhibitor (PAI-I)166 and tissue inhibitor of metalloendoproteinase (TIMP).165 Most studies have reported that TGFβl exerts an inhibitory effect on fibroblast proliferation.167
A serum miRNAs signature for early diagnosis of bladder cancer
Published in Annals of Medicine, 2023
Zuhu Yu, Chong Lu, Yongqing Lai
The function annotation of the target genes was analyzed with Enrichr database and illustrated in Figure 5. Go analysis revealed that these genes were mostly enriched in intracellular membrane-bounded organelle, nucleus, intracellular vesicle, cyclin/CDK positive transcription elongation factor complex, serine/threonine kinase complex. Molecular function of the target genes was enriched in regulation of transcription, cellular response to transforming growth factor beta stimulus. Biological process of the target genes involved was enriched in sequence-specific DNA binding, protein serine/threonine kinase activator activity, cyclin-dependent protein serine/threonine kinase activator activity, ubiquitin-like protein ligase binding. KEGG pathway analysis indicated the target genes enriched in FOXO signaling pathway, MAPK signaling pathway, Relaxin signaling pathway, Hepatocellular carcinoma, pathways in cancer. The functional annotation implied that target genes of the three miRNAs may be involved in proliferation and progression of bladder cancer.
Genotoxicity evaluation of self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG), a novel siRNA nanoparticle for the treatment of fibrotic disease
Published in Drug and Chemical Toxicology, 2022
Hyeon-Young Kim, Tae Rim Kim, Sung-Hwan Kim, In-Hyeon Kim, Youngho Ko, Sungil Yun, In-Chul Lee, Han-Oh Park, Jong-Choon Kim
Transforming growth factor-beta (TGF-β) plays a pivotal role, in the progression of pulmonary fibrosis; it is involved in fibroblast proliferation, epithelial-mesenchymal transition, and extracellular matrix deposition (Mauviel 2005, Wynn 2008, Li et al. 2016, Luo et al. 2016). It has been reported that TGF-β induce amphiregulin (AREG) and an epithelial growth factor receptor ligand, and siRNA silencing of AR attenuated TGF-β-induced pulmonary fibrosis (Zhou et al. 2012, Lee et al. 2014). Recently, self-assembled-micelle inhibitory RNA-targeting AREG (SAMiRNA-AREG) nanoparticles have been found to safely deliver siRNA against target genes and effectively restore pulmonary function in an animal model with bleomycin-induced pulmonary fibrosis (Yoon et al. 2016). Although efficacy evaluation for pulmonary fibrosis has been performed, other toxicological features such as genotoxicity have not been previously explored.
The role of the Notch pathway in the pathogenesis of systemic sclerosis: clinical implications
Published in Expert Review of Clinical Immunology, 2021
Filipe Seguro Paula, José Delgado Alves
Even though the contribution of Notch signaling to fibroblast activation and heightened fibrogenesis seems to be clear, it should not be analyzed in an isolated fashion nor should that mechanism be considered specific for SSc. Transforming growth factor beta (TGF-β) is the main inducer of the remodeling of the connective tissue during wound healing as well as in many fibrotic pathologic changes [30]. Not surprisingly, it is more abundant in the skin of SSc patients and fibroblasts can synthesize and secrete it leading to a ‘TGF-β autocrine hypothesis’ on SSc fibrosis [7]. In fact, fibroblasts isolated from the skin of SSc patients remain activated in vitro even after several culture passages, in a pure culture milieu [26], suggesting a perpetuation of the fibrogenic response based on autocrine factors. However, inhibition of TGF-β only partially reverts the pathological changes seen in SSc fibroblasts in vitro [31], supporting the notion that, even though TGF-β may be sufficient to induce the full fibroblast activation program, once it is set in motion other factors may perpetuate the response. Mechanotransduction of cell-matrix interactions mediated by integrins and focal adhesion kinase (FAK) may be involved in the perpetuation of this response, as it has been shown that FAK is a main activator of YAP/TAZ (Yes-associated protein/transcriptional coactivator with PDZ-binding motif) effectors, and both function independently in the non-canonical activation of the TGF-β signaling pathway and fibrogenesis [32,33]. Interestingly, YAP/TAZ can also interact with various components of the Notch pathway [34].
Related Knowledge Centers
- Cell Signaling
- Protease
- White Blood Cell
- Cytokine
- Transforming Growth Factor Beta Superfamily
- Tgf Beta 1
- Tgf Beta 2
- Transforming Growth Factor, Beta 3
- Serine/Threonine-Specific Protein Kinase
- Tgf Beta Receptor