Cyclic Peptide-Based Biologics Regulating HGF-MET
Abstract
:1. Introduction
2. Cyclic Peptides and RaPID System
3. HiP-8 (HGF-Inhibitory Peptide-8)
3.1. Background
3.2. Discovery and Specificity
3.3. Inhibition of Molecular Dynamics
3.4. Potential Application
4. Synthetic MET Agonists Based on Cyclic Peptides
4.1. Discovery
4.2. MET Activation and Biological Activities
5. HGF-mimetics (MET-agonists) and Potential Applications
5.1. MET Agonists with Different Molecular Characteristics
5.2. Potential Applications
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AFM | atomic force microscopy |
ALS | amyotrophic lateral sclerosis |
FIT | flexible in vitro translation |
HGF | hepatocyte growth factor |
MET | mesenchymal-epithelial transition factor |
HiP-8 | HGF-inhibitory peptide-8 |
PET | positron emission tomography |
RaPID | random non-standard peptide integrated discovery |
scHGF | single-chain HGF |
tcHGF | two-chain HGF |
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Organ | Target Cells | Characteristics | References |
---|---|---|---|
Liver | Hepatocytes | Highly susceptible to apoptosis after liver injury. Impairment in recovery from liver necrosis after liver injury. Steatotic change of the liver in aged mice. Decrease in mitotic hepatocytes and delayed regeneration after partial hepatectomy. | [39,40,41,42,43,44,45,46,47] |
Hepatoblastic (oval) cells | Increased apoptosis, decreased migration, and decreased population in hepatoblastic cells. Impaired differentiation into hepatocytes. | ||
Kupffer cells α-SMA+/CK19+ cells Bone marrow-derived immune cells | Increased reactive oxygen species and oxidative stress. Earlier and faster progression of steatohepatitis and earlier and stronger progression of fibrosis in dietary model for steatohepatitis. | ||
Kidney | Tubular cells | Aggravated renal injury and inflammation after acute kidney injury. | [48,49,50,51] |
Podocytes | Severe podocyte injury and apoptosis, and albuminuria after toxic injury. | ||
Collecting duct cells | Increased tubular necrosis and interstitial fibrosis following unilateral ureteral obstruction. | ||
Ureteric bud | Reduction in nephron number. | ||
Skin | Keratinocytes | Lack of keratinocyte migration after skin wound. Severe impairment epidermal wound closure. | [52] |
Pancreas | β-Cell | Loss of acute-phase insulin secretion in response to glucose, and impaired glucose tolerance. Diminished glucose tolerance and reduced plasma insulin after a glucose challenge. Susceptible to streptozotocin-induced diabetes | [53,54,55] |
Nervous system | All neural cells Forebrain neurons Dorsal pallial neurons | Deficit in contextual fear condition. Reduced volume of cortical tissue. Hyperconnectivity in circuit-specific intracortical neurons. Alteration of neuron architecture. Excitatory hyperconnectivity and hypoactivity. Increases proximal and reduces distal apical dendritic branching of neocortical pyramidal neurons in post-pubertal period. | [56,57,58,59,60,61,62,63] |
Cerebral cortex and hippocampus neurons | Enhanced long-term potentiation (LTP) and long-term depression (LTD) at early developmental stages. Reduced LTP and LTD at young adult stage. Larger size in the rostral cortex, caudal hippocampus, dorsal striatum, thalamus, and corpus callosum. | ||
Ganglionic eminence | Increased numbers of striatal GABAergic interneurons in the lateral sensorimotor. Delayed procedural learning. | ||
Myenteric plexus neurons | Reduced length of neurites and increased bowel injury. | ||
Lung | Alveolar type II cells | Impaired airspace formation caused by reductions in alveolar epithelial cell growth and survival. | [64] |
Heart | Cardiomyocytes | Cardiomyocyte hypertrophy and interstitial fibrosis by 6 months. Systolic cardiac dysfunction by 9 months. Accumulated reactive oxygen species and imbalance in the antioxidant defenses. | [65] |
Immune system | Dendritic cells | Failure to emigrate toward lymph nodes during inflammation. Impaired contact hypersensitivity reaction. | [66,67,68] |
Neutrophils | Increased tumor growth and metastasis. | ||
T-cells | Acceleration of age-related thymic involution. | ||
Muscle | Satellite cells | Defective muscle regeneration in response to injury. | [69] |
Breast | Mammary epithelial cells | Defects in branching in mammary glands. | [70] |
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Sato, H.; Imamura, R.; Suga, H.; Matsumoto, K.; Sakai, K. Cyclic Peptide-Based Biologics Regulating HGF-MET. Int. J. Mol. Sci. 2020, 21, 7977. https://doi.org/10.3390/ijms21217977
Sato H, Imamura R, Suga H, Matsumoto K, Sakai K. Cyclic Peptide-Based Biologics Regulating HGF-MET. International Journal of Molecular Sciences. 2020; 21(21):7977. https://doi.org/10.3390/ijms21217977
Chicago/Turabian StyleSato, Hiroki, Ryu Imamura, Hiroaki Suga, Kunio Matsumoto, and Katsuya Sakai. 2020. "Cyclic Peptide-Based Biologics Regulating HGF-MET" International Journal of Molecular Sciences 21, no. 21: 7977. https://doi.org/10.3390/ijms21217977