Therapeutic potential of hepatocyte growth factor against cerebral ischemia (Review).

Wen Zeng,Meng Mao,Rong Ju

doi:10.3892/etm.2014.2133

Abstract

The effective treatment for cerebral ischemia has not yet been established. Hepatocyte growth factor (HGF) is a potent pleiotropic cytokine that is involved in cell and tissue regeneration, including in the central nervous system. Studies have demonstrated that an exogenous administration of HGF protects brain tissue from ischemic damage. In response to binding to the receptor c-Met, HGF activates the downstream signaling pathways (including the phosphatidylinositol 3-kinase/Akt, Ras/MAPK and signal transducer and activator of transcription pathways) which leads to various cellular responses involved in angiogenesis, glial scar formation, anti-apoptosis and neurogenesis. The purpose of this review is to summarize the present understanding of the therapeutic potential of HGF in cerebral ischemia.

Highlights

Y1235) within the activation loop of the tyrosine kinase domain, which regulate the intrinsic kinase activity of c‐Met
This leads to the activation of downstream signaling pathways including the PI3K/Akt, Ras/MAPK and signal transducer and activator of transcription (STAT) pathways [19,20,21]
Other studies demonstrated that vascular endothelial growth factor (VEGF), a notable proangiogenic factor [28], increases vascular density, reduces brain damage and improves neurological deficits [29,30,31,32], suggesting that angiogenic therapy may be helpful for ischemic brain injury

Summary

Introduction

Y1235) within the activation loop of the tyrosine kinase domain, which regulate the intrinsic kinase activity of c‐Met. Angiogenesis was first described as a vital factor in tumor growth in 1971 [22] and defined as the formation of new vessels sprouting from pre‐existing capillaries in the pathological or physiological processes in adult tissue [23]. It may be highly regulated by the action of growth factors, proteolytic enzymes or other extracellular matrix factors that stimulate the growth of endothelial cells. Attempts to alleviate ischemic cerebral injuries and ameliorate the prognosis have focused on ensuring or improving the survival of neurons, while ignoring the role of angiogenesis. By activating the specific receptor, c‐Met, HGF induces DNA synthesis and proliferation of vascular endothelial cells through MAPK/ERK and STAT3 pathway activation [39,40]

Objectives

Methods

Conclusion