Role Of TGF-?1/Smad Signaling Pathway In Vascular Injury Of Retinopathy Of Prematurity

Objectives: To explore the changes and effects of TGF-?1/Smad signaling pathway in Phase 1 of retinopathy of prematurity and provide new targets for early intervention of ROP.Methods:1.Rat 50/10 OIR models were established.Then immunohistochemistry was used to compare the expression and distribution of TGF-?1 in the retina of OIR and control groups in D2,D4,D6,D10 and D14.2.Human umbilical vein endothelial cells were cultured in vitro,and the experiment group was treated with hyperoxia-induced complete medium and hypoxia-induced complete medium intermittently.Wound healing kinetic and transwell migration assay were used to test the proliferation and migration abilities of HUVEC.RT-q PCR was used to detect the m RNA relative expression of TGF-?1,and Western blotting was used to detect the expression of p Smad2/3 in cells of two groups.Results:1.The results of Rat retinal immunohistochemistry showed that the expression level of TGF-?1 in OIR group was higher than that in control group on D2 and D4,and the expression was not significantly different on D6 in both groups.In D10 and D14,the expression level of TGF-?1 in OIR group was lower than in control group.Furthermore,the expression of TGF-?1 focused on the ganglion cell layer.In OIR group,it appeared no TGF-?1 in the outer plexiform layer.2.After hyperoxia/hypoxia stimulation of HUVEC,the cell's morphology changed,and the ability of proliferation and migration decreased.3.In RT-q PCR,the relative expression of m RNA in TGF-?1 after 2 and 3 cycles of stimulation was higher than that in the control group.After 4 cycles of stimulation,the expression of TGF-?1 in the experiment group was lower than that in the control group.4.In Western blotting,after several cycles of stimulation,the expression of pSmad2/3 in experiment group was significantly lower than that in control group,and it was statistically significant.Conclusions: In the rat 50/10 OIR model and hyperoxia/hypoxia HUVEC model,the expression levels of TGF-?1 increased firstly and then decreased in experiment group.In the cell model,the expression of p Smad2/3 was significantly reduced after the stimulation,along with the decrease of cell proliferation and migration ability,which indicated that the decreased of TGF-?1/Smad2/3 signaling pathway would lead to the decrease of angiogenesis.The pathway may participate in the inhibition of angiogenesis in Phase 1 of ROP.