Lymphangiogenesis is essential for the development of the lymphatic system and is important for physiological processes such as homeostasis, metabolism and immunity. Cellular communication network fac Show more
Lymphangiogenesis is essential for the development of the lymphatic system and is important for physiological processes such as homeostasis, metabolism and immunity. Cellular communication network factor 2 (CCN2, also known as CTGF), is a modular and matricellular protein and a well-known angiogenic factor in physiological and pathological angiogenesis. However, its roles in lymphangiogenesis and intracellular signaling in lymphatic endothelial cells (LECs) remain unclear. Here, we investigated the effects of CCN2 on lymphangiogenesis. In in vivo Matrigel plug assays, exogenous CCN2 increased the number of Podoplanin-positive vessels. Subsequently, we found that CCN2 induced phosphorylation of ERK in primary cultured LECs, which was almost completely inhibited by the blockade of integrin αvβ5 and partially decreased by the blockade of integrin αvβ3. CCN2 promoted direct binding of ERK to dual-specific phosphatase 6 (DUSP6), which regulated the activation of excess ERK by dephosphorylating ERK. In vitro, CCN2 promoted tube formation in LECs, while suppression of Dusp6 further increased tube formation. In vivo, immunohistochemistry also detected ERK phosphorylation and DUSP6 expression in Podoplanin-positive cells on CCN2-supplemented Matrigel. These results indicated that CCN2 promotes lymphangiogenesis by enhancing integrin αvβ5-mediated phosphorylation of ERK and demonstrated that DUSP6 is a negative regulator of excessive lymphangiogenesis by CCN2. Show less
The present study was conducted to analyze biochemical marker genes and to clarify genetic variation in 4 Mongolian gerbil (Meriones unguiculatus) strains (MGS/Sea, MON/Jms Gbs, Kwl: Mongolian Gerbil Show more
The present study was conducted to analyze biochemical marker genes and to clarify genetic variation in 4 Mongolian gerbil (Meriones unguiculatus) strains (MGS/Sea, MON/Jms Gbs, Kwl: Mongolian Gerbil and Hos: Mongolian gerbil) maintained in Japan. Cellulose acetate, starch gel or agar gel electrophoresis was used. Of the 23 kinds of proteins detected, variation was found only in liver acid phosphatase (Acp2); no variation in other proteins was found within or among strains. The results suggest that these 4 Mongolian gerbil strains are genetically similar. A strain difference was found in the Acp2 locus of liver acid phosphatase. The Kwl: Mongolian Gerbil strain had a band of Acp2 locus, whereas MGS/Sea, MON/Jms and Hos: Mongolian gerbil strains did not. Show less