Hepatocyte Growth Factor Isoforms in Tissue Repair, Cancer, and Fibrotic Remodeling
Hepatocyte growth factor (HGF), also known as scatter factor (SF), is a pleotropic factor required for normal organ development during embryogenesis. In the adult, basal expression of HGF maintains tissue homeostasis and is up-regulated in response to tissue injury. HGF expression is necessary for t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2014-11-01
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| Series: | Biomedicines |
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| Online Access: | http://www.mdpi.com/2227-9059/2/4/301 |
| _version_ | 1831805073515085824 |
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| author | Ognoon Mungunsukh Elizabeth A. McCart Regina M. Day |
| author_facet | Ognoon Mungunsukh Elizabeth A. McCart Regina M. Day |
| author_sort | Ognoon Mungunsukh |
| collection | DOAJ |
| description | Hepatocyte growth factor (HGF), also known as scatter factor (SF), is a pleotropic factor required for normal organ development during embryogenesis. In the adult, basal expression of HGF maintains tissue homeostasis and is up-regulated in response to tissue injury. HGF expression is necessary for the proliferation, migration, and survival of epithelial and endothelial cells involved in tissue repair in a variety of organs, including heart, lung, kidney, liver, brain, and skin. The administration of full length HGF, either as a protein or using exogenous expression methodologies, increases tissue repair in animal models of tissue injury and increases angiogenesis. Full length HGF is comprised of an N-terminal hairpin turn, four kringle domains, and a serine protease-like domain. Several naturally occurring alternatively spliced isoforms of HGF were also identified. The NK1 variant contains the N-terminal hairpin and the first kringle domain, and the NK2 variant extends through the second kringle domain. These alternatively spliced forms of HGF activate the same receptor, MET, but they differ from the full length protein in their cellular activities and their biological functions. Here, we review the species-specific expression of the HGF isoforms, their regulation, the signal transduction pathways they activate, and their biological activities. |
| first_indexed | 2024-12-22T19:18:23Z |
| format | Article |
| id | doaj.art-6c97d3160b0f45c09af6435f86827ba8 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-12-22T19:18:23Z |
| publishDate | 2014-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-6c97d3160b0f45c09af6435f86827ba82022-12-21T18:15:27ZengMDPI AGBiomedicines2227-90592014-11-012430132610.3390/biomedicines2040301biomedicines2040301Hepatocyte Growth Factor Isoforms in Tissue Repair, Cancer, and Fibrotic RemodelingOgnoon Mungunsukh0Elizabeth A. McCart1Regina M. Day2Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USADepartment of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USADepartment of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USAHepatocyte growth factor (HGF), also known as scatter factor (SF), is a pleotropic factor required for normal organ development during embryogenesis. In the adult, basal expression of HGF maintains tissue homeostasis and is up-regulated in response to tissue injury. HGF expression is necessary for the proliferation, migration, and survival of epithelial and endothelial cells involved in tissue repair in a variety of organs, including heart, lung, kidney, liver, brain, and skin. The administration of full length HGF, either as a protein or using exogenous expression methodologies, increases tissue repair in animal models of tissue injury and increases angiogenesis. Full length HGF is comprised of an N-terminal hairpin turn, four kringle domains, and a serine protease-like domain. Several naturally occurring alternatively spliced isoforms of HGF were also identified. The NK1 variant contains the N-terminal hairpin and the first kringle domain, and the NK2 variant extends through the second kringle domain. These alternatively spliced forms of HGF activate the same receptor, MET, but they differ from the full length protein in their cellular activities and their biological functions. Here, we review the species-specific expression of the HGF isoforms, their regulation, the signal transduction pathways they activate, and their biological activities.http://www.mdpi.com/2227-9059/2/4/301hepatocyte growth factorNK1NK2MET receptorsignal transductiontruncated isoformstissue repair |
| spellingShingle | Ognoon Mungunsukh Elizabeth A. McCart Regina M. Day Hepatocyte Growth Factor Isoforms in Tissue Repair, Cancer, and Fibrotic Remodeling Biomedicines hepatocyte growth factor NK1 NK2 MET receptor signal transduction truncated isoforms tissue repair |
| title | Hepatocyte Growth Factor Isoforms in Tissue Repair, Cancer, and Fibrotic Remodeling |
| title_full | Hepatocyte Growth Factor Isoforms in Tissue Repair, Cancer, and Fibrotic Remodeling |
| title_fullStr | Hepatocyte Growth Factor Isoforms in Tissue Repair, Cancer, and Fibrotic Remodeling |
| title_full_unstemmed | Hepatocyte Growth Factor Isoforms in Tissue Repair, Cancer, and Fibrotic Remodeling |
| title_short | Hepatocyte Growth Factor Isoforms in Tissue Repair, Cancer, and Fibrotic Remodeling |
| title_sort | hepatocyte growth factor isoforms in tissue repair cancer and fibrotic remodeling |
| topic | hepatocyte growth factor NK1 NK2 MET receptor signal transduction truncated isoforms tissue repair |
| url | http://www.mdpi.com/2227-9059/2/4/301 |
| work_keys_str_mv | AT ognoonmungunsukh hepatocytegrowthfactorisoformsintissuerepaircancerandfibroticremodeling AT elizabethamccart hepatocytegrowthfactorisoformsintissuerepaircancerandfibroticremodeling AT reginamday hepatocytegrowthfactorisoformsintissuerepaircancerandfibroticremodeling |