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Hynda K. Kleinman,김경순,강훈희 한국응용생명화학회 2018 Applied Biological Chemistry (Appl Biol Chem) Vol.61 No.6
The thin extracellular matrix that is found basally in epithelial and endothelial cells and around smooth muscle, peripheral nerves, and fat cells is known as the basement membrane. A murine tumor matrix extract, termed Matrigel, has provided an abundant source of basement membrane proteins (laminin, collagen IV, heparan sulfate, etc.). Matrigel gels at room temperature into a structure similar to the authentic matrix. Embryonic tissue explants, stem cells, and various cell types differentiate when cultured on Matrigel. Matrigel has been used in various in vitro assays for angiogenesis, cell invasion, spheroid formation, organoid formation from a single cell, etc. In vivo Matrigel improves/promotes tumor xenograft growth and is used to measure angiogenesis, improve heart and spinal cord repair, increase tissue transplant take, etc. Endothelial cells plated on top of Matrigel form capillarylike tubules. The gene for thymosin beta 4 was induced at 4 h after plating endothelial cells on Matrigel, and when the thymosin beta 4 protein was added exogenously to the culture, tubule formation was accelerated. Thymosin beta 4, a small 43 kDa protein present in all body fluids and cells, has multiple biological activities, including reducing inflammation, apoptosis, and cytotoxicity while increasing cell migration, stem cell recruitment and differentiation, and tissue repair. Thymosin beta 4 was subsequently found to promote angiogenesis in vivo and to improve dermal and ocular healing in experimental injury models. It has regenerative activity in animal models of traumatic brain injury, stroke, multiple sclerosis, heart attack, peripheral neuropathy, liver and kidney fibrosis, and hair growth. Clinical trials have demonstrated its efficacy for both stasis and pressure ulcers and for both dry eye and a rare ocular disease. This mini review will discuss the development of Matrigel and the discovery of thymosin beta 4 as a regenerative protein that is upregulated when endothelial cells are plated on Matrigel.
Over-expression of thymosin beta4 promotes abnormal tooth development and stimulation of hair growth
Cha, Hee-Jae,Philp, Deborah,Lee, Soo-Hyun,Moon, Hye-Sung,Kleinman, Hynda K.,Nakamura, Takashi UPV/EHU Press 2010 The International journal of developmental biology Vol.54 No.1
<P>Thymosin beta 4 has multi-functional roles in cell physiology. It accelerates wound healing, hair growth and angiogenesis, and increases laminin-5 expression in corneal epithelium. Furthermore, thymosin beta 4 stimulates tumor growth and metastasis by induction of cell migration and vascular endothelial growth factor-mediated angiogenesis. Using a construct on the skin-specific keratin-5 promoter, we have developed thymosin beta 4 over-expressing transgenic mice to further study its functional roles. Thymosin beta 4 in adult skin and in embryonic stages of the transgenic mouse was analyzed by both Western blot and immunohistochemistry. The over-expression of thymosin beta 4 was observed especially around hair follicles and in the teeth in the transgenic mice. We examined the phenotype of the thymosin beta 4 over-expressing mice. Hair growth was accelerated. In addition, the transgenic mice had abnormally-shaped white teeth and dull incisors. We found that the expression of laminin-5 was up-regulated in the skin of the transgenic mice. We conclude that thymosin beta 4 has an important physiological role in hair growth and in tooth development.</P>