The Research Of The Effects Of Fibroblast Growth Factor 9 And Its Receptor On Corneal Endothelial Cells

Purpose:Fibroblast growth factor 9(FGF9)is a member of FGF family.Its main receptor is fibroblast growth factor receptor 3(FGFR3).FGF9 plays an important role in the development of various tissues and the healing of injuries.However,whether FGF9 and FGFR3 are expressed on corneal endothelial cells(CECs)and their effects are unknown.Therefore,our research is aimed to detect the expression and effects of FGF9 and FGFR3 on CECsMethods:To detect the expression of FGF9 and FGFR3 on the normal corneal endothelial cells of human and rabbit in vivo.At the sam time,to check the expression in the process of healing after injuries on rabbits and cultured rabbit corneal endothelial cells of different passages by immunohistochemistry,PCR,western blot and so on.At the same time,to check the expressions of cell junctions,morphology and functions under the same circumstances.On the other hand,to check the effects of exogenous FGF9 on cell junctions,morphology and functions of cultured CECs from different passages.Finally,to test the effects of FGF9 on the endothelial-mesenchymal-transition induced by FGF2Results:FGF9 and FGFR3 are widely expressed on human and rabbit corneal endothelial cells(CECs)in vivo.In the healing process after injuries in rabbit CECs,the expression of EndMT marker a-SMA is upregulated in the first 4 days and downregulated after 7 days.In contrast,the expression of FGF9 and FGFR3 is downregulated in the first 4 days and upregulated after 7 days.In the process of culturing CECs ex vivo,the expression of FGF9,FGFR3,cell junction and function markers are downregulated with continuous passages,but the expression of EndMT marker a-SMA is upregulated little by little.When the cultured CECs are treated with exogenous FGF9,it can reverse the EndMT process by keeping normal cell morphology,upregulating cell junction and function markers and downregulating EndMT markera-SMA and vimentin.Morever,FGF9 can also reverse the EndMT process induced by FGF2.Conclusions:FGF9 and its receptor FGFR3 are expressed on corneal endothelial cells,they play important roles in the regulation of cell morphology,junctions and functions,and reverse the process of EndMT to maintain normal cell state.Our research is the first to find the expressions and effects of FGF9 and its receptor FGFR3 on corneal endothelial cells.Our research also provides some new understanding on corneal endothelial morphology and function.At the same time,our discovery may give new strategies and directions and lay a foundation in the treatment of corneal endothelial injuries and the construction of tissue engineering of corneal endothelial.Morever,our discoveries inspires us to do some researches on other FGF family memrbers.