Accessibility Statement Skip Navigation
  • Resources
  • Blog
  • Journalists
  • +44 (0)20 7454 5110
  • Client Login
  • Send a Release
Return to PR Newswire homepage
  • News
  • Products
  • Contact
When typing in this field, a list of search results will appear and be automatically updated as you type.

Searching for your content...

No results found. Please change your search terms and try again.
  • News in Focus
      • Browse News Releases

      • All Public Company News
      • All Multimedia News
      • View All News Releases

      • Regulatory News

      • D/A/CH Regulatory News
      • UK Regulatory News
      • View All Regulatory News

  • Business & Money
      • Auto & Transportation

      • Aerospace & Defense
      • Air Freight
      • Airlines & Aviation
      • Automotive
      • Maritime & Shipbuilding
      • Railroads & Intermodal Transportation
      • Supply Chain/Logistics
      • Transportation, Trucking & Railroad
      • Travel
      • Trucking & Road Transportation
      • View All Auto & Transportation

      • Business Technology

      • Blockchain
      • Broadcast Tech
      • Computer & Electronics
      • Computer Hardware
      • Computer Software
      • Data Analytics
      • Electronic Commerce
      • Electronic Components
      • Electronic Design Automation
      • Financial Technology
      • High Tech Security
      • Internet Technology
      • Nanotechnology
      • Networks
      • Peripherals
      • Semiconductors
      • View All Business Technology

      • Entertain­ment & Media

      • Advertising
      • Art
      • Books
      • Entertainment
      • Film & Motion Picture
      • Magazines
      • Music
      • Publishing & Information Services
      • Radio & Podcast
      • Television
      • View All Entertain­ment & Media

      • Financial Services & Investing

      • Accounting News & Issues
      • Acquisitions, Mergers & Takeovers
      • Banking & Financial Services
      • Bankruptcy
      • Bond & Stock Ratings
      • Conference Call Announcements
      • Contracts
      • Cryptocurrency
      • Dividends
      • Earnings
      • Earnings Forecasts & Projections
      • Financing Agreements
      • Insurance
      • Investments Opinions
      • Joint Ventures
      • Mutual Funds
      • Private Placement
      • Real Estate
      • Restructuring & Recapitalisation
      • Sales Reports
      • Shareholder Activism
      • Shareholder Meetings
      • Stock Offering
      • Stock Split
      • Venture Capital
      • View All Financial Services & Investing

      • General Business

      • Awards
      • Commercial Real Estate
      • Corporate Expansion
      • Earnings
      • Environmental, Social and Governance (ESG)
      • Human Resource & Workforce Management
      • Licensing
      • New Products & Services
      • Obituaries
      • Outsourcing Businesses
      • Overseas Real Estate (non-US)
      • Personnel Announcements
      • Real Estate Transactions
      • Residential Real Estate
      • Small Business Services
      • Socially Responsible Investing
      • Surveys, Polls & Research
      • Trade Show News
      • View All General Business

  • Science & Tech
      • Consumer Technology

      • Artificial Intelligence
      • Blockchain
      • Cloud Computing/Internet of Things
      • Computer Electronics
      • Computer Hardware
      • Computer Software
      • Consumer Electronics
      • Cryptocurrency
      • Data Analytics
      • Electronic Commerce
      • Electronic Gaming
      • Financial Technology
      • Mobile Entertainment
      • Multimedia & Internet
      • Peripherals
      • Social Media
      • STEM (Science, Tech, Engineering, Math)
      • Supply Chain/Logistics
      • Wireless Communications
      • View All Consumer Technology

      • Energy & Natural Resources

      • Alternative Energies
      • Chemical
      • Electrical Utilities
      • Gas
      • General Manufacturing
      • Mining
      • Mining & Metals
      • Oil & Energy
      • Oil & Gas Discoveries
      • Utilities
      • Water Utilities
      • View All Energy & Natural Resources

      • Environ­ment

      • Conservation & Recycling
      • Environmental Issues
      • Environmental Policy
      • Environmental Products & Services
      • Green Technology
      • Natural Disasters
      • View All Environ­ment

      • Heavy Industry & Manufacturing

      • Aerospace & Defence
      • Agriculture
      • Chemical
      • Construction & Building
      • General Manufacturing
      • HVAC (Heating, Ventilation & Air-Conditioning)
      • Machinery
      • Machine Tools, Metalworking & Metallurgy
      • Mining
      • Mining & Metals
      • Paper, Forest Products & Containers
      • Precious Metals
      • Textiles
      • Tobacco
      • View All Heavy Industry & Manufacturing

      • Telecomm­unications

      • Carriers & Services
      • Mobile Entertainment
      • Networks
      • Peripherals
      • Telecommunications Equipment
      • Telecommunications Industry
      • VoIP (Voice over Internet Protocol)
      • Wireless Communications
      • View All Telecomm­unications

  • Lifestyle & Health
      • Consumer Products & Retail

      • Animals & Pets
      • Beers, Wines & Spirits
      • Beverages
      • Bridal Services
      • Cannabis
      • Cosmetics & Personal Care
      • Fashion
      • Food & Beverages
      • Furniture & Furnishings
      • Home Improvement
      • Household, Consumer & Cosmetics
      • Household Products
      • Jewellery
      • Non-Alcoholic Beverages
      • Office Products
      • Organic Food
      • Product Recalls
      • Restaurants
      • Retail
      • Supermarkets
      • Toys
      • View All Consumer Products & Retail

      • Entertain­ment & Media

      • Advertising
      • Art
      • Books
      • Entertainment
      • Film & Motion Picture
      • Magazines
      • Music
      • Publishing & Information Services
      • Radio & Podcast
      • Television
      • View All Entertain­ment & Media

      • Health

      • Biometrics
      • Biotechnology
      • Clinical Trials & Medical Discoveries
      • Dentistry
      • FDA Approval
      • Fitness/Wellness
      • Health Care & Hospitals
      • Health Insurance
      • Infection Control
      • International Medical Approval
      • Medical Equipment
      • Medical Pharmaceuticals
      • Mental Health
      • Pharmaceuticals
      • Supplementary Medicine
      • View All Health

      • Sports

      • General Sports
      • Outdoors, Camping & Hiking
      • Sporting Events
      • Sports Equipment & Accessories
      • View All Sports

      • Travel

      • Amusement Parks & Tourist Attractions
      • Gambling & Casinos
      • Hotels & Resorts
      • Leisure & Tourism
      • Outdoors, Camping & Hiking
      • Passenger Aviation
      • Travel Industry
      • View All Travel

  • Policy & Public Interest
      • Policy & Public Interest

      • Animal Welfare
      • Corporate Social Responsibility
      • Economic News, Trends & Analysis
      • Education
      • Environmental
      • European Government
      • Labour & Union
      • Natural Disasters
      • Not For Profit
      • Public Safety
      • View All Policy & Public Interest

  • People & Culture
      • People & Culture

      • Aboriginal, First Nations & Native American
      • African American
      • Asian American
      • Children
      • Diversity, Equity & Inclusion
      • Hispanic
      • Lesbian, Gay & Bisexual
      • Men's Interest
      • People with Disabilities
      • Religion
      • Senior Citizens
      • Veterans
      • Women
      • View All People & Culture

  • Overview
  • Distribution
  • Paid Placement
  • Multichannel Amplification
  • Disclosure Services
  • SocialBoost
  • Rooms
    • MediaRoom
    • ESG Rooms
  • AI Tools
  • General Enquiries
  • Media Enquiries
  • Partnerships
  • Hamburger menu
  • Cision PR Newswire UK provides press release distribution, targeting, monitoring, and marketing services
  • Send a Release
    • Phone

    • +44 (0)20 7454 5110 from 8 AM - 5:30 PM GMT

    • ALL CONTACT INFO
    • Contact Us

      +44 (0)20 7454 5110
      from 8 AM - 5:30 PM GMT

  • Client Login
  • Send a Release
  • Resources
  • Blog
  • Journalists
  • News in Focus
    • Browse News Releases
    • Regulatory News
  • Business & Money
    • Auto & Transportation
    • Business Technology
    • Entertain­ment & Media
    • Financial Services & Investing
    • General Business
  • Science & Tech
    • Consumer Technology
    • Energy & Natural Resources
    • Environ­ment
    • Heavy Industry & Manufacturing
    • Telecomm­unications
  • Lifestyle & Health
    • Consumer Products & Retail
    • Entertain­ment & Media
    • Health
    • Sports
    • Travel
  • Policy & Public Interest
    • Policy & Public Interest
  • People & Culture
    • People & Culture
  • Client Login
  • Send a Release
  • Resources
  • Blog
  • Journalists
  • Overview
  • Distribution
  • Paid Placement
  • Multichannel Amplification
  • Disclosure Services
  • Cision Communications Cloud®
  • AI Tools
  • Client Login
  • Send a Release
  • Resources
  • Blog
  • Journalists
  • General Enquiries
  • Media Enquiries
  • Partnerships
  • Client Login
  • Send a Release
  • Resources
  • Blog
  • Journalists

Kanazawa University Research: Scientists Successfully Obtain Synthetic Growth Factor Compatible to the Native Protein


News provided by

Kanazawa University

29 Jan, 2019, 04:31 GMT

Share this article

Share toX

Share this article

Share toX

KANAZAWA, Japan, January 29, 2019 /PRNewswire/ --

In a recent study published in Scientific Reports, researchers at Kanazawa University show that an artificially synthesized molecule can exhibit compatible activities to natural molecules in its biological effectiveness. 

Continue Reading
This image opens in the lightbox
HGF (Hepatocyte Growth Factor) is a bioactive protein which exerts biological activities through the binding and activation of the MET transmembrane receptor. (PRNewsFoto/Kanazawa University)
This image opens in the lightbox
HGF activates MET receptor and activation of MET receptor triggers intracellular signaling leading to the enhancement of cell division, migration, survival, and 3-D tubulogenesis (PRNewsFoto/Kanazawa University)
This image opens in the lightbox
Epithelial tubulogenesis (blanching duct formation) is critical for functional tissue architecture in several organs, including kidney, mammary gland, lung, and bile duct. (PRNewsFoto/Kanazawa University)

     (Photo: https://mma.prnewswire.com/media/814734/Main_Fig_Outline_of_discovery.jpg )

     (Photo: https://mma.prnewswire.com/media/814735/Fig_1_HGF_in_regeneration.jpg )

     (Photo: https://mma.prnewswire.com/media/814736/Fig_2_3D_tubulogenesis.jpg )

Growth factors are ligands that play important roles in the body - they are responsible for tissue regeneration, wound healing, and the maintenance and growth of cells. Stimulating growth factor-dependent pathways is therefore an important therapeutic strategy to promote the regeneration of tissues due to injuries and diseases. Using synthetic substitutes of growth factors is the primary method for artificially stimulating the desired pathways. However, synthetic substitutes are often not as efficient and comprehensive in inducing the required biological changes. Kunio Matsumoto at Kanazawa University and colleagues have recently created a substitute for one such growth factor, that produces a comparable biological response.

The hepatocyte growth factor (HGF) binds to and activates a receptor, known as MET (Fig. 1). In other words, HGF is a native ligand for the MET receptor. The MET receptor is a transmembrane protein. Upon extracellular binding of HGF to the extracellular region of MET, pairing of the receptors (called 'dimerization') occurs, which allows the intracellular chemical change of the receptors (called 'phosphorylation'). This receptor phosphorylation means receptor activation, which triggers activation of intracellular biological signal transduction pathways, leading to a variety of biological responses in cells.

To mimic the actions of HGF, the researchers created a 'macrocyclic peptide' molecule (named aMD5-PEG11) which activates the MET receptor (Main Fig). This molecule is composed of chemically cross-linked two macrocyclic peptides. Such cyclic molecules are flexible in structure and can bind and activate MET. Furthermore, aMD5-PEG11 docked onto to a different region of MET than HGF, aMD-PEG11 and HGF therefore did not directly compete for MET and nullify each other's effects. Whether aMD-PEG11 also induced these structural changes, was then assessed in two different human cell types. aMD-PEG11 induced the same extent of coupling/dimerization and phosphorylation of the MET receptor in a comparable ability to HGF.

If the structural changes induced by HGF and aMD5-PEG11 were similar, were the biological effects similar too? MET activation by HGF induces migration of cells. This migration was also observed by aMD-PEG11. MET activation by HGF also results in activation of other signaling proteins such as AKT and ERK. aMD-PEG11 also had comparable effects on the activation of these molecules. These effects were cancelled when a specific inhibitor for MET was added, indicating that these effects were definitely results of MET activation induced by aMD-PEG11 or HGF.

The activation of a set of genes is responsible for specific biological functions. When the genes activated by aMD-PEG11 and HGF were respectively analyzed during 3-D tubulogenesis in human kidney cells induced by aMD5-PEG11 and HGF, changes in the gene expression profiles were largely overlapped and comparable between HGF and aMD5-PEG11. Because 3-D tubulogenesis by HGF in kidney cells implicates construction/development and re-construction/regeneration of a functional kidney, the comparable ability between HGF and aMD5-PEG11 to induce gene expression profiles suggests that aMD5-PEG11 can facilitate regeneration of the kidney in a potential comparable to HGF (Fig. 2).

Several growth factors have been used as biological drugs manufactured by recombinant protein production. This study reported a synthetic artificial ligand that induced chemical and biological effects equivalent to a natural ligand. Not only are artificial ligands relatively cheaper to produce, but often their smaller size leads to greater permeability in the body. "Artificial MET receptor agonists such as macrocyclic peptides have the potential to be developed as novel biological drugs manufactured by chemical synthesis," concludes the team. Besides growth factors, this strategy can be applied to many kinds of ligands.

Background 

Ligands and receptors: Ligands are molecules in the cell that specifically but reversibly bind to another molecule, known as its receptor. This binding of the two is the important first step in the activation of a series of pathways, responsible for a biological response. Ligands usually induce chemical/structural changes on the receptors subsequent to binding. Common examples of ligands are enzymes, neurotransmitters, hormones and growth factors.

Synthesizing drugs that mimic ligands and bind to specific receptors is a common strategy in medicine to stimulate the activation of biological pathways.

Reference 

Wenyu Miao, Katsuya Sakai, Naoya Ozawa, Takumi Nishiuchi, Yoshinori Suzuki, Kenichiro Ito, Tomomi Morioka, Masataka Umitsu, Junichi Takagi, Hiroaki Suga and Kunio Matsumoto. Cellular signaling and gene expression profiles evoked by a bivalent macrocyclic peptide that serves as an artificial MET receptor agonist. Scientific Reports, 07 November 2018.

DOI 

https://doi.org/10.1038/s41598-018-34835-4

HGF (Hepatocyte Growth Factor) is a bioactive protein which exerts biological activities through the binding and activation of the MET transmembrane receptor. The extracellular binding of HGF to MET receptor induces association of two MET receptors (called "dimerization"), thereby the MET receptor can be activated. Activation of the MET receptor results in biological responses of cells, including cell proliferation, migration, survival, and 3-D tubulogenesis/morphogenesis. Because of these multiple biological activities, HGF supports regeneration of tissues and phase-II clinical trials recombinant HGF protein for treatment of patients with spinal cord injury and amyotrophic lateral sclerosis (ALS) are ongoing. HGF is composed of 697 amino acids and manufactured by recombinant protein technology as a biological drug. The authors discovered artificial HGF composed of chemically linked two cyclic peptides (aMD5-PEG11). This artificial peptide HGF can bind and activate MET receptor, in a comparable ability to HGF, a native ligand for MET receptor. Because artificial peptide HGF has biological activities compatible to HGF and it can be manufactured by chemical synthesis that can be manufactured at much lower cost compared to recombinant protein production, artificial peptide HGF is expected to be a next-generation biological drug manufactured by chemical synthesis. Moreover, the technology used to discover artificial peptide HGF can be fundamental technology for discovery of artificial peptide cytokines and growth factors for medical application.

HGF activates MET receptor and activation of MET receptor triggers intracellular signaling leading to the enhancement of cell division, migration, survival, and 3-D tubulogenesis. These biological activities lead to the regeneration of tissues after injuries and diseases.

Epithelial tubulogenesis (blanching duct formation) is critical for functional tissue architecture in several organs, including kidney, mammary gland, lung, and bile duct. In the culture of normal human kidney tubular cells in 3-D collagen gel, artificial HGF/aMD5-PEG11, as well as HGF, dynamically induce tubulogenesis. This biological activity is unique to HGF-MET receptor pathway. Therefore, artificial peptide HGF capable of activating MET in a comparable ability to HGF may be applicable to regeneration-based medicine as a new biological drug candidate.

About Kanazawa University 

http://www.kanazawa-u.ac.jp/e/

As the leading comprehensive university on the Sea of Japan coast, Kanazawa University has contributed greatly to higher education and academic research in Japan since it was founded in 1949. The University has three colleges and 17 schools offering courses in subjects that include medicine, computer engineering, and humanities.

The University is located on the coast of the Sea of Japan in Kanazawa - a city rich in history and culture. The city of Kanazawa has a highly respected intellectual profile since the time of the fiefdom (1598-1867). Kanazawa University is divided into two main campuses: Kakuma and Takaramachi for its approximately 10,200 students including 600 from overseas.

Further information:
Hiroe Yoneda
Vice Director of Public Affairs
WPI Nano Life Science Institute (WPI-NanoLSI)
Kanazawa University
Kakuma-machi, Kanazawa 920-1192, Japan
Email: nanolsi-office@adm.kanazawa-u.ac.jp
Tel: +81(76)234-4550

Modal title

Also from this source

Kanazawa University research: From hydration layers to nanoarchitectures: Water's pivotal role in peptide organization on 2D nanomaterials

Researchers at the Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, report in Small, a weekly peer-reviewed scientific journal...

Kanazawa University research: High-speed AFM and 3D modelling help towards understanding the dynamics of a protein implicated in several cancers

Researchers at the Nano Life Science Institute (WPI-NanoLSI), Kanazawa University observe and model how the enzyme ADAR1 interacts with...

More Releases From This Source

Explore

Biotechnology

Biotechnology

Health Care & Hospitals

Health Care & Hospitals

Medical Pharmaceuticals

Medical Pharmaceuticals

STEM (Science, Tech, Engineering, Math)

STEM (Science, Tech, Engineering, Math)

News Releases in Similar Topics

Contact PR Newswire

  • +44 (0)20 7454 5110
    from 8 AM - 5:30 PM GMT
  • General Enquiries
  • Media Enquiries
  • Partnerships

Products

  • Content Distribution
  • Multimedia Services
  • Disclosure Services
  • Cision Communications Cloud®

About

  • About PR Newswire
  • About Cision
  • Partnering Opportunities
  • Careers
  • Accessibility Statement
  • APAC
  • APAC - Simplified Chinese
  • APAC - Traditional Chinese
  • Brazil
  • Canada
  • Czech
  • Denmark
  • Finland
  • France
  • Germany
  • India
  • Indonesia
  • Israel
  • Japan
  • Korea
  • Mexico
  • Middle East
  • Middle East - Arabic
  • Netherlands
  • Norway
  • Poland
  • Portugal
  • Russia
  • Slovakia
  • Spain
  • Sweden
  • United States
  • Vietnam

My Services

  • All News Releases
  • Customer Portal
  • Resources
  • Blog
  • Journalists
  • Data Privacy

Do not sell or share my personal information:

  • Submit via Privacy@cision.com 
  • Call Privacy toll-free: 877-297-8921

Contact PR Newswire

Products

About

My Services
  • All News Releases
  • Customer Portal
  • Resources
  • Blog
  • Journalists
+44 (0)20 7454 5110
from 8 AM - 5:30 PM GMT
  • Terms of Use
  • Privacy Policy
  • Information Security Policy
  • Site Map
  • RSS
  • Cookie Settings
Copyright © 2025 PR Newswire Europe Limited. All Rights Reserved. A Cision company.