SDS

Hepatocyte growth factor is described as a HPR-binding growth factor, due to having angiogenic abilities. HGF is secreted by fibroblasts, and while it is known for being mitogenic for epithelial cells, it has no impact on the fibroblasts. It is also known as Scatter factor.

InteractionsResearch has shown that hepatocyte growth factor does interact with c-Met oncogene. This protein product, also known as the HGF receptor HFGR. Autocrine activation and overexpression of the receptor protein have both been connected to oncogenesis. Furthermore more the growth factor also has been shown to interact with dermatan sulfate and glycosaminoglycans heparan sulfate. The interaction between heparan sulfate is particularly important as it enables the hepatocyte growth factor to form a c-Met that is complex in form. This leads to key processes including cell migration and cell division, due to being able to transduce intracellular signals. Certain modulators of Hepatocyte Growth Factor are also apparent such as Dihexa. This is a centrally penetrant small molecule compound and it bonds directly to HGF. In doing so, the orally active compound is able increase the power of c-Met.

MechanismsHGF is a paracrine cellular growth, morphogenic, and motility factor. It targets and acts upon epithelial and endothelial cells after it has been secreted by mesenchymal cells. However, it can also act on haematopoietic progenitor cells, and T-cells. It has been shown through research that it has some outstanding impacts on wound healing, adult organ regeneration, and in embryonic organ development. Plasma levels in patients with advanced heart failure have also been shown to have high levels of HGF.

Structure The protein is a single inactive polypeptide. It is split by serine proteases to form to different chains, the 34-kDa beta-chain and the 69-kDa alpha-chain. This then causes a disulfide bond between the two chains and ultimate produces the heterodimeric molecule which is active. This protein is part of the plasminogen subfamily. However, it has no protease activity detectable.

FunctionHGF plays an important role in liver and kidney repair. As well as this, it also has some part to play in the process of bone metastasizing. Further than this, it may play a role in bone remodelling and repair due to its nature as a mitogenic for cells of certain areas such as osteoblasts, and osteoclasts. HGF has also been linked to renal repair and recovery and neuro-oncology. It is thought that it can prevent tubule damage by activating the antiapoptotic pathways, at the same times as promoting adhesion of certain tubular cells to the basement membrane. This is believed to be the case as HGF has important impacts on the proliferation of cells.Studies have also implicated HGF in a range of different forms of cancer. This includes the lungs, thyroid, colon, pancreas and breast. Interestingly, local expression of HGF found in the breast is also connected to macromastia. As well as this, it is a crucial part of typical mammary gland development.

Research is currently ongoing, exploring the potential for using the hepatocyte growth factor and its receptor c-met to discover a treatment for diseases such as Parkinson’s and Alzheimer’s.