scholarly journals Computational Biophysical, Biochemical, and Evolutionary Signature of Human R-Spondin Family Proteins, the Member of Canonical Wnt/β-Catenin Signaling Pathway

2014 ◽  
Vol 2014 ◽  
pp. 1-22 ◽  
Author(s):  
Ashish Ranjan Sharma ◽  
Chiranjib Chakraborty ◽  
Sang-Soo Lee ◽  
Garima Sharma ◽  
Jeong Kyo Yoon ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Computational Algorithm ◽  
Biophysical Properties ◽  
Glycosylation Sites ◽  
Peptide Length ◽  
Basic Understanding ◽  
Therapeutic Properties ◽  
The Common ◽  
Canonical Wnt ◽  
Positively Charged

In human, Wnt/β-catenin signaling pathway plays a significant role in cell growth, cell development, and disease pathogenesis. Four human (Rspo)s are known to activate canonical Wnt/β-catenin signaling pathway. Presently, (Rspo)s serve as therapeutic target for several human diseases. Henceforth, basic understanding about the molecular properties of (Rspo)s is essential. We approached this issue by interpreting the biochemical and biophysical properties along with molecular evolution of (Rspo)s thorough computational algorithm methods. Our analysis shows that signal peptide length is roughly similar in (Rspo)s family along with similarity in aa distribution pattern. In Rspo3, four N-glycosylation sites were noted. All members are hydrophilic in nature and showed alike GRAVY values, approximately. Conversely, Rspo3 contains the maximum positively charged residues while Rspo4 includes the lowest. Four highly aligned blocks were recorded through Gblocks. Phylogenetic analysis shows Rspo4 is being rooted with Rspo2 and similarly Rspo3 and Rspo1 have the common point of origin. Through phylogenomics study, we developed a phylogenetic tree of sixty proteins (n=60) with the orthologs and paralogs seed sequences. Protein-protein network was also illustrated. Results demonstrated in our study may help the future researchers to unfold significant physiological and therapeutic properties of (Rspo)s in various disease models.

scholarly journals Inhibition of the canonical Wnt signaling pathway by a β-catenin/CBP inhibitor prevents heart failure by ameliorating cardiac hypertrophy and fibrosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thanachai Methatham ◽  
Shota Tomida ◽  
Natsuka Kimura ◽  
Yasushi Imai ◽  
Kenichi Aizawa
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Left Ventricular ◽  
Cardiac Wall ◽  
Macrophage Marker ◽  
Glycolysis Pathway ◽  
Canonical Wnt ◽  
Macrophage Accumulation

AbstractIn heart failure (HF) caused by hypertension, the myocyte size increases, and the cardiac wall thickens. A low-molecular-weight compound called ICG001 impedes β-catenin-mediated gene transcription, thereby protecting both the heart and kidney. However, the HF-preventive mechanisms of ICG001 remain unclear. Hence, we investigated how ICG001 can prevent cardiac hypertrophy and fibrosis induced by transverse aortic constriction (TAC). Four weeks after TAC, ICG001 attenuated cardiac hypertrophy and fibrosis in the left ventricular wall. The TAC mice treated with ICG001 showed a decrease in the following: mRNA expression of brain natriuretic peptide (Bnp), Klf5, fibronectin, β-MHC, and β-catenin, number of cells expressing the macrophage marker CD68 shown in immunohistochemistry, and macrophage accumulation shown in flow cytometry. Moreover, ICG001 may mediate the substrates in the glycolysis pathway and the distinct alteration of oxidative stress during cardiac hypertrophy and HF. In conclusion, ICG001 is a potential drug that may prevent cardiac hypertrophy and fibrosis by regulating KLF5, immune activation, and the Wnt/β-catenin signaling pathway and inhibiting the inflammatory response involving macrophages.

Canonical Wnt/β-Catenin Signaling Pathway Is Dysregulated in Patients With Primary and Secondary Myelofibrosis

2016 ◽  
Vol 16 (9) ◽  
pp. 523-526 ◽  
Author(s):  
Marko Lucijanic ◽  
Ana Livun ◽  
Cedna Tomasovic-Loncaric ◽  
Tajana Stoos-Veic ◽  
Vlatko Pejsa ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Secondary Myelofibrosis ◽  
Canonical Wnt

scholarly journals Nodes, paranodes and neuropathies

2017 ◽  
Vol 89 (1) ◽  
pp. 61-71 ◽  
Author(s):  
Janev Fehmi ◽  
Steven S Scherer ◽  
Hugh J Willison ◽  
Simon Rinaldi
Keyword(s):  
Peripheral Nerves ◽  
Clinical Importance ◽  
Specific Cell ◽  
Peripheral Neuropathies ◽  
Autoimmune Neuropathy ◽  
Basic Understanding ◽  
Clinical Variants ◽  
Inflammatory Neuropathies ◽  
The Common ◽  
Treatment Responsiveness

This review summarises recent evidence supporting the involvement of the specialised nodal and perinodal domains (the paranode and juxtaparanode) of myelinated axons in the pathology of acquired, inflammatory, peripheral neuropathies.The identification of new target antigens in the inflammatory neuropathies heralds a revolution in diagnosis, and has already begun to inform increasingly targeted and individualised therapies. Rapid progress in our basic understanding of the highly specialised nodal regions of peripheral nerves serves to strengthen the links between their unique microstructural identities, functions and pathologies. In this context, the detection of autoantibodies directed against nodal and perinodal targets is likely to be of increasing clinical importance. Antiganglioside antibodies have long been used in clinical practice as diagnostic serum biomarkers, and associate with specific clinical variants but not to the common forms of either acute or chronic demyelinating autoimmune neuropathy. It is now apparent that antibodies directed against several region-specific cell adhesion molecules, including neurofascin, contactin and contactin-associated protein, can be linked to phenotypically distinct peripheral neuropathies. Importantly, the immunological characteristics of these antibodies facilitate the prediction of treatment responsiveness.

scholarly journals The Regulation of Bone Metabolism and Disorders by Wnt Signaling

2019 ◽  
Vol 20 (22) ◽  
pp. 5525 ◽  
Author(s):  
Kazuhiro Maeda ◽  
Yasuhiro Kobayashi ◽  
Masanori Koide ◽  
Shunsuke Uehara ◽  
Masanori Okamoto ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Wnt Signaling ◽  
Bone Metabolism ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Osteoporosis Treatment ◽  
Biological Phenomena ◽  
Approximate Molecular Weight ◽  
Skeletal Disorders ◽  
Canonical Wnt

Wnt, a secreted glycoprotein, has an approximate molecular weight of 40 kDa, and it is a cytokine involved in various biological phenomena including ontogeny, morphogenesis, carcinogenesis, and maintenance of stem cells. The Wnt signaling pathway can be classified into two main pathways: canonical and non-canonical. Of these, the canonical Wnt signaling pathway promotes osteogenesis. Sclerostin produced by osteocytes is an inhibitor of this pathway, thereby inhibiting osteogenesis. Recently, osteoporosis treatment using an anti-sclerostin therapy has been introduced. In this review, the basics of Wnt signaling, its role in bone metabolism and its involvement in skeletal disorders have been covered. Furthermore, the clinical significance and future scopes of Wnt signaling in osteoporosis, osteoarthritis, rheumatoid arthritis and neoplasia are discussed.

AB0070 Wnt and wisp1 expression in the synovium induces cartilage damage by skewing of tgf-beta signaling via the canonical wnt signaling pathway

2013 ◽  
Vol 72 (Suppl 3) ◽  
pp. A807.1-A807
Author(s):  
M. H. van den Bosch ◽  
A. B. Blom ◽  
P. L. van Lent ◽  
H. M. van Beuningen ◽  
F. A. van de Loo ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Cartilage Damage ◽  
Wnt Signaling Pathway ◽  
Tgf Beta ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt
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