scholarly journals The tyrosine kinase receptors Ron and Sea control "scattering" and morphogenesis of liver progenitor cells in vitro.

1996 ◽  
Vol 7 (4) ◽  
pp. 495-504 ◽  
Author(s):  
E Medico ◽  
A M Mongiovi ◽  
J Huff ◽  
M A Jelinek ◽  
A Follenzi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Progenitor Cells ◽  
Type I Collagen ◽  
Growth Factor Receptor ◽  
Biological Response ◽  
Tyrosine Kinase Receptors ◽  
Type I ◽  
Macrophage Stimulating Protein

The mammalian RON and the avian sea genes encode tyrosine kinase receptors of poorly characterized biological functions. We recently identified macrophage-stimulating protein as the ligand for Ron; no ligand has yet been found for Sea. In this work we investigated the biological response to macrophage-stimulating protein in mouse liver progenitor cells expressing Ron. These cells were also transfected with a chimeric cDNA encoding the cytoplasmic domain of Sea, fused to the extracellular domain of Trk (nerve growth factor receptor). In the presence of nanomolar concentrations of the respective ligands, both receptors induced cell "scattering", extracellular matrix invasion, and DNA synthesis. When liver progenitor cells were grown in a tri-dimensional type-I collagen matrix, ligand-induced stimulation of either Ron or Sea induced sprouting of branched cell cords, evolving into ductular-like tubules. The motogenic, mitogenic, and morphogenic responses were also elicited by triggering the structurally related hepatocyte growth factor receptor (Met) but not epidermal growth factor or platelet-derived growth factor receptors. These data show that Ron, Sea, and Met belong to a receptor subfamily that elicits a distinctive biological response in epithelial cells.

scholarly journals Inhibition of tyrosine kinase receptor signaling attenuates fibrogenesis in an ex vivo model of human renal fibrosis

2020 ◽  
Vol 318 (1) ◽  
pp. F117-F134 ◽  
Author(s):  
Emilia Bigaeva ◽  
Elisabeth G. D. Stribos ◽  
Henricus A. M. Mutsaers ◽  
Bram Piersma ◽  
Anna M. Leliveld ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Renal Fibrosis ◽  
Collagen Type ◽  
Growth Factor Receptor ◽  
Collagen Type I ◽  
Renal Tissue ◽  
Tyrosine Kinase Receptors ◽  
Type I

Poor translation from animal studies to human clinical trials is one of the main hurdles in the development of new drugs. Here, we used precision-cut kidney slices (PCKS) as a translational model to study renal fibrosis and to investigate whether inhibition of tyrosine kinase receptors, with the selective inhibitor nintedanib, can halt fibrosis in murine and human PCKS. We used renal tissue of murine and human origins to obtain PCKS. Control slices and slices treated with nintedanib were studied to assess viability, activation of tyrosine kinase receptors, cell proliferation, collagen type I accumulation, and gene and protein regulation. During culture, PCKS spontaneously develop a fibrotic response that resembles in vivo fibrogenesis. Nintedanib blocked culture-induced phosphorylation of platelet-derived growth factor receptor and vascular endothelial growth factor receptor. Furthermore, nintedanib inhibited cell proliferation and reduced collagen type I accumulation and expression of fibrosis-related genes in healthy murine and human PCKS. Modulation of extracellular matrix homeostasis was achieved already at 0.1 μM, whereas high concentrations (1 and 5 μM) elicited possible nonselective effects. In PCKS from human diseased renal tissue, nintedanib showed limited capacity to reverse established fibrosis. In conclusion, nintedanib attenuated the onset of fibrosis in both murine and human PCKS by inhibiting the phosphorylation of tyrosine kinase receptors; however, the reversal of established fibrosis was not achieved.

Recent Advances on Epidermal Growth Factor Receptor as a Molecular Target for Breast Cancer Therapeutics

2020 ◽  
Vol 21 ◽  
Author(s):  
Swathi R. Shetty ◽  
Ragini Yeeravalli ◽  
Tanya Bera ◽  
Amitava Das
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Critical Role ◽  
Growth Factor Receptor ◽  
Type I ◽  
Egfr Inhibition ◽  
Epidermal Growth

: Epidermal growth factor receptor (EGFR), a type-I transmembrane protein with intrinsic tyrosine kinase activity is activated by peptide growth factors such as EGF, epigen, amphiregulin, etc. EGFR plays a vital role in regulating cell growth, migration, and differentiation in various tissue-specific cancers. It has been reported to be overexpressed in lung, head, and neck, colon, brain, pancreatic, and breast cancer that trigger tumor progression and drug resistance. EGFR overexpression alters the signaling pathway and induces cell division, invasion, and cell survival. Our prior studies demonstrated that EGFR inhibition modulates chemosensitivity in breast cancer stem cells thereby serving as a potential drug target for breast cancer mitigation. Tyrosine kinase inhibitors (Lapatinib, Neratinib) and monoclonal antibodies (Trastuzumab) targeting EGFR have been developed and approved by the US FDA for clinical use against breast cancer. This review highlights the critical role of EGFR in breast cancer progression and enumerates the various approaches being undertaken to inhibit aggressive breast cancers by suppressing the downstream pathways. Further, the mechanisms of action of potential molecules at various stages of drug development as well as clinically approved drugs for breast cancer treatment are illustrated.

scholarly journals In Vitro and In Silico Studies of Quercetin and Daidzin as Selective Anticancer Agents

2021 ◽  
Vol 21 (2) ◽  
pp. 310
Author(s):  
Muhammad Sulaiman Zubair ◽  
Syariful Anam ◽  
Saipul Maulana ◽  
Muhammad Arba
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Molecular Docking ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Growth Factor Receptor ◽  
In Silico Studies ◽  
Epidermal Growth

Quercetin and daidzin are flavonoid and flavonoid glycoside type compounds that have been found in many plants and nutraceuticals. This study aims to examine the in vitro cytotoxic and selectivity properties of quercetin and daidzin on breast and cervical cancers and to study their molecular interaction and stability on epidermal growth factor receptor tyrosine kinase (EGFR-TK) by applying molecular docking and molecular dynamics (MD) simulations. In vitro anticancer activity was performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method on breast cancer cell (T47D), cervical cancer cells (HeLa), and Vero normal cells, while molecular docking and MD simulation were done by using AutoDock Vina and Amber18 package software, respectively. Quercetin and daidzin showed potent cytotoxic and high selectivity on both cell lines. Daidzin was found to has a higher IC50 and selectivity index than quercetin. Docking and MD results showed that both compounds prefer to interact with epidermal growth factor receptor tyrosine kinase (EGFR-TK). Daidzin showed better interaction than quercetin with a docking score of -9.6 kcal/mol. Also, daidzin was found more stable than quercetin with low RMSD and RMSF values.

scholarly journals Properties of the beta-nerve growth factor receptor in development.

1975 ◽  
Vol 67 (1) ◽  
pp. 118-125 ◽  
Author(s):  
K Herrup ◽  
E M Shooter
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Biological Response ◽  
Nerve Growth Factor Receptor ◽  
Cell Surface Receptor ◽  
Sensory Ganglia ◽  
Binding Assays ◽  
Nerve Growth

The cell surface receptor for beta-nerve growth factor was used as a probe to study the development of embryonic chick sensory ganglia. The ganglia were shown to lose their responsiveness to nerve growth factor in vitro between 14 and 16 days of embryonic age. This loss occurred by a decrease in the magnitude of the maximum biological response, not by a shifting of the response to higher concentrations. Binding assays for the beta-nerve growth factor receptor, using 125I-radiolabelled beta-nerve growth factor, were performed with cells from sensory ganglia 8, 12, 14, 16, 18, and 21 days of age. The assays revealed a twofold increase in the number of receptor sites per ganglion between 8 and 14 days and a sixfold drop between 14 and 16 days of embryonic life. Neither increase nor decrease was accompanied by a large change in the affinity of the receptor for the protein. Together with the results of the bioassay, the data show that the loss of biological responsiveness is correlated with and may be due to a loss of the cells' ability to bind beta-nerve growth factor. Correlation of the results of the binding assays with the known ontogeny of the chick embryo provides a hint at the role of nerve growth factor in normal development.

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