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Mechanotransduction in Cardiovascular Development and Regeneration: A Genetic Zebrafish Model
Published in Juhyun Lee, Sharon Gerecht, Hanjoong Jo, Tzung Hsiai, Modern Mechanobiology, 2021
Rongsong Li, Kyung In Baek, Chih-Chiang Chang, Bill Zhou, Tzung Hsiai
Canonical Wnt/β-catenin signaling is a pivotal pathway regulating development, cell proliferation, and migration [74]. We further demonstrated that shear stress–stimulated Ang-2 expression is mediated by the canonical Wnt signaling pathway. While a Wnt agonist, Wnt3a, promoted Ang-2 expression, inhibition of Wnt signaling with Dickkopfs-1 (Dkk-1) or IWR-1 inhibited EC migration and tube formation. In the heat-shock-inducible Dkk-1 transgenic (Tg(hsp70l: Dkk1-GFP)) zebrafish embryos, Ang-2b (zebrafish Ang-2) expression was downregulated upon heat shock. Ang-2 MO injection into transgenic Tg(kdrl: GFP) zebrafish caused downregulation of Ang-2, resulting in the impaired development of subintestinal vessels (SIV) at 72 hours after fertilization. Inhibition of Wnt signaling also inhibited the SIV development that is rescued with Ang-2 mRNA. In the zebrafish tail amputation model, inhibition of Wnt signaling retarded and reduced the rate of vascular regeneration that is also rescued by Ang-2 mRNA [72]. These findings support the notion that the mechanosensitive Wnt/Ang-2 pathway modulates vascular development and regeneration.
Osteoimmunomodulation with Biomaterials
Published in Nihal Engin Vrana, Biomaterials and Immune Response, 2018
Bengü Aktaş, Bora Garipcan, Zehra Betül Ahi, Kadriye Tuzlakoğlu, Emre Ergene, Pınar Yılgör Huri
Apart from these, there is another pathway called Wnt signalling that is considered a key regulator for bone formation. According to studies, OPG expression is mediated by the Wnt signalling pathway [71,72]. The binding of Wnt signalling molecules activates two different signalling pathways, known as the β/catenin-dependent canonical and independent non-canonical pathway. The β/catenin-dependent canonical pathway has an essential role in promoting the differentiation of osteoblast precursor cells to mature osteoblasts. In a similar manner, this pathway has the property of suppressing bone resorption by changing the RANKL/OPG ratio [73]. In the study of Diarra et al., they indicate that TNF-mediated expression of Dickkopf-1 (DKK1) suppress Wnt signalling, thus this action hamper bone formation, meanwhile bone resorption is increased with the expression of RANKL in an inflammatory arthritis condition. Therefore, the blockade of DKK-1 induces bone formation since Wnt proteins are able to induce OPG expression [71]. On the other hand, Maeda et al. showed that Wnt5a, which is a non-canonical Wnt ligand, expressed by osteoblast-lineage cells, enhanced RANK expression through Ror-2 signalling in osteoclast precursors, thereby enhancing osteoclastogenesis, by effecting JNK and c-Jun pathways on the promoter of encoding RANK in both physiological and pathological conditions [74]. The above findings reveal that bone mass is commonly regulated by the combination of two signalling pathways; RANK/RANKL and Wnt/β-catenin.
Engineered Extracellular Vesicle-Based Therapeutics for Liver Cancer
Published in Peixuan Guo, Kirill A. Afonin, RNA Nanotechnology and Therapeutics, 2022
The expression of EpCAM is associated with the Wnt/β-catenin pathway which can control the proliferation of hepatic stem cells (Yamashita et al. 2007; Li et al. 2016; Katoh 2017). β-catenin stabilization has been associated with tumor-initiating cells or CSC renewal. EpCAM positive cell populations isolated from AFP positive HCC have hepatic CSC-like properties with the capacity of self-renewal and differentiation and feature activation of Wnt/β-catenin signaling (Yamashita et al. 2009). Furthermore, silencing of β-catenin by siRNA could inhibit proliferation and self-renewal characteristics of liver CSC derived from CD133(+) sphere forming cells in vitro and in vivo (Quan et al. 2013).
Regulation of stem cell fate and function by using bioactive materials with nanoarchitectonics for regenerative medicine
Published in Science and Technology of Advanced Materials, 2022
Wei Hu, Jiaming Shi, Wenyan Lv, Xiaofang Jia, Katsuhiko Ariga
For commonly used covalently crosslinked hydrogels, the dynamic mechanical properties are often derived from cell-mediated degradation. Khetan et al. encapsulated human mesenchymal stem cells (hMSCs) in covalently crosslinked hyaluronic acid hydrogels subjected to a multi-step crosslinking protocol, from cell–mediated–degradable to non-degradable [126]. They demonstrate that the differentiation of hMSCs is directed by the generation of traction force mediated through cellular degradation of matrix. Furthermore, their work emphasizes the type of hydrogel underlying the mechanism by which stem cells respond to biophysical cues. Heilshorn et al. demonstrate that the maintenance of neural progenitor cell (NPC) stemness in 3D hydrogels is dependent on matrix degradability but interestingly is independent of cytoskeletal tension and integrin-binding ligand clustering [127]. According to their work, the underlying mechanism is increased cadherin-mediated cell–cell contact and activating β-catenin signalling. Moreover, they demonstrate that NPC proliferation and differentiation also require increased degradability. Following this study, they further clarify the role of matrix remodelling on NPC differentiation and maturation [128]. Permitting 7-day matrix remodelling prior to induction of differentiation, NPCs can differentiate into astrocytes or mature functional neurons. It is attributed to up-regulating YAP expression via cadherin-mediated cell–cell contact.
Atmospheric fine particulate matter and epithelial mesenchymal transition in pulmonary cells: state of the art and critical review of the in vitro studies
Published in Journal of Toxicology and Environmental Health, Part B, 2020
Margaux Cochard, Frédéric Ledoux, Yann Landkocz
The most involved pathways include the TGF-β superfamily with formation of complex SMAD2/3 and SMAD4 (Kolosova, Nethery, and Kern 2011; Valcourt et al. 2005) and its translocation through the nucleus, activation of TNF receptor-associated factor 6 (TRAF6) followed by stimulation of p38 MAPK and JUN N-terminal kinase (JNK) (Kolosova, Nethery, and Kern 2011; Yamashita et al. 2008), and the phosphatidylinositol 3-kinases (PI3K) through the PI3K/protein kinase B (AKT)/β-catenin pathway (Bakin et al. 2000; Lamouille et al. 2012; Wang et al. 2014). The PI3K/AKT/β-catenin pathway is also linked to Wnt, integrins and tyrosine kinase receptors pathways. In this pathway, activation of AKT inhibits glycogen synthase kinase-3β (GSK-3β) (Bachelder et al. 2005) to stabilize β-catenin. β-catenin is therefore able to translocate in the nucleus to engage lymphoid enhancer-binding factor 1 (LEF) (Nawshad et al. 2007) and T cell factor (TCF) which promote EMT transcription factors (Lamouille, Xu, and Derynck 2014).
Callyspongia samarensis (Porifera) extracts exhibit anticancer activity and induce bleaching in Porites cylindrica (Scleractinia)
Published in Chemistry and Ecology, 2018
Miguel Azcuna, Jortan O. Tun, Helen T. Yap, Gisela P. Concepcion
Coral and human proteomes have common cell signalling pathways, like Wnt/β-catenin and NF-κβ-STAT pathways [23]. The Wnt/β-catenin pathway impacts cell processes like cell proliferation, fate determination, morphology, polarity, and motility. Wnts also regulate stem cell proliferation and may control the fate of cancer stem cells [24]. The NF-κβ protein complex is involved in the transcription of DNA and activates the expression of genes, such as anti-apoptotic and mitogenic genes [25]. In cancer cells, these signalling pathways may become misregulated or overexpressed, and several anticancer compounds from marine organisms have demonstrated an ability to act on such pathways [26]. Therefore, compounds in HPLC fraction 8 may act on the Wnt/β-catenin and NF-κβ-STAT pathways to induce necrosis in coral cells or inhibit growth in cancer cell lines. Furthermore, due to the symbiotic association of coral and dinoflagellates (the zooxanthellae), the latter, which are responsible for the photosynthetic machinery of the coral, will perish as a result of tissue necrosis in the coral. This can explain the lower MQY in nubbins that were exposed to experimental gels with HPLC fraction 8.