Effect of Snake Venom Disintegrin like domain on the Homing of Mesenchymal Stem Cells

Mesenchymal stem cells have many advantages as grafts for cell transplantation. The homing of MSCs after systemic infusion is still poorly understood. This report explored the effect of the combination of BM-MSCs with Disintegrin like fraction obtained from Cerastes cerastes crude venom on the fibrotic liver of CCl4 treated mice. It was observed that Disintegrin like fraction could increase homing of BM-MSCs labeled with the PKH26 into the liver tissue of CCl4 treated mice. A significant decrease in AST and ALT serum levels after administration of Disintegrin like fraction and/or BM-MSCs in CCl4 treated mice were detected. VEGF was expressed in mice injected with CCl4 alone, followed by Disintegrin like fraction or both Disintegrin like fraction and BM-MSCs. β- catenin was expressed in mice injected with CCl4 alone, followed by BM-MSCs or both BM-MSCs and Disintegrin like fraction. Caspase-3 gene was expressed in CCl4 treated mice injected with BM-MSCs or both BM-MSCs and Disintegrin like fraction. TNF-α and HO-1 were expressed in all groups. Administration of Disintegrin like fraction and / or BM-MSCs improved the histo-pathological picture and showed signs of regeneration in CCl4 induced liver fibrosis. In conclusion, Disintegrin like fraction could increase homing of BM-MSCs into the liver tissue of CCl4 treated mice. Further studies need to be done to explore the mechanism of homing caused by Disintegrin

Glycoprotein hormone receptors: link between receptor homodimerization and negative cooperativity

The monomeric model of rhodopsin-like G protein-coupled receptors (GPCRs) has progressively yielded the floor to the concept of GPCRs being oligo(di)mers, but the functional correlates of dimerization remain unclear. In this report, dimers of glycoprotein hormone receptors were demonstrated in living cells, with a combination of biophysical (bioluminescence resonance energy transfer and homogenous time resolved fluorescence/fluorescence resonance energy transfer), functional and biochemical approaches. Thyrotropin (TSHr) and lutropin (LH/CGr) receptors form homo- and heterodimers, via interactions involving primarily their heptahelical domains. The large hormone-binding ectodomains were dispensable for dimerization but modulated protomer interaction. Dimerization was not affected by agonist binding. Observed functional complementation indicates that TSHr dimers may function as a single functional unit. Finally, heterologous binding-competition studies, performed with heterodimers between TSHr and LH/CG–TSHr chimeras, demonstrated the unsuspected existence of strong negative cooperativity of hormone binding. Tracer desorption experiments indicated an allosteric behavior in TSHr and, to a lesser extent, in LH/CGr and FSHr homodimers. This study is the first report of homodimerization associated with negative cooperativity in rhodopsin-like GPCRs. As such, it may warrant revisitation of allosterism in the whole GPCR family