| Objective: Pelvic organ prolapse(POP)refers to a group of diseases in which female pelvic floor supporting tissues are weak and pelvic organs prolapse from the pelvic cavity.Pelvic organ prolapse is related to the relaxation of pelvic floor supporting ligament.Knowing more about the pathogenesis of this disease,can delay the disease process,reduce the pain of patients,so as to achieve good clinical significance.According to the previous research results,we speculate that the abnormal expression of IGF-1 may be related to the pathogenesis of pelvic organ prolapse.According to the results of bioinformatics analysis,we predicted that Lnc00839 and IGF-1 may have a targeted regulatory relationship,which affecting the collagen expression of fibroblasts.This paper aims to detect the relationship between IGF-1and Lnc00839 and the relationship between Lnc00839 and pelvic organ prolapse,in order to find the molecular biological mechanism of pelvic organ prolapse,and provide potential methods for early diagnosis and early intervention of the disease.Methods: 1.PCR and Western-blot were used to detect the expression of Lnc00839,mi R-19-3p,IGF-1,IGF-1R,COL-1 and COL-3 in vaginal wall tissue of prolapse group and control group,and to analyze the correlation with the clinical severity of organ prolapse.2.Analysis of apoptosis and autophagy in the prolapse group and the control group: TUNEL was used to detect the apoptosis between the two groups,and Western blot was used to detect the expression of autophagy markers Beclin1,LC3 II / I and apoptosis markers Bax,Bcl-2.3.After IGF-1 was up-regulated,the expression of COL-1and LC3 II / I was detected.After lnc00839 was up-regulated,the expression of IGF-1and IGF-1R was detected.4.To verify the targeting relationship between Lnc00839 and mi R-19-3p.5.To verify the targeting relationship between mi R-19-3p and IGF-1.6.Western-blot was used to detect the expression of Akt,m TOR,p70s6 k,p-Akt,p-m TOR,p-p70s6 k in the prolapse group and the control group.7.The expression of downstream pathway proteins Akt,m TOR,P70S6 K,p-Akt,p-m TOR and p-p70s6 k were detected after the fibroblasts were transfected with lnc00839 and different concentrations of IGF-1was added.Results: 1.The expression levels of Lnc00839,COL-1,IGF-1 and IGF-1R in the vaginal wall of POP patients were decreased,and the expression level was negatively correlated with the severity of pelvic organ prolapse,while the expression level of mi R-19-3p was increased,and the expression level was positively correlated with the severity of pelvic organ prolapse.2.The levels of autophagy and apoptosis in the vaginal wall of the POP group are increased.IGF-1 can promote the secretion of COL-1 by inhibiting the excessive autophagy.3.Lnc00839 can up-regulate the expression of IGF-1 in vaginal wall fibroblasts.4.Lnc00839 can bind to mi R-19-3p.5.mi R-19-3p can bind to IGF-1 to inhibit the up-regulation of downstream IGF-1 and COL-1 by Lnc00839.mi R-19-3p regulates the expression of COL-1 in fibroblasts by promoting apoptosis and excessive autophagy.6.Akt-m TOR-p70s6 k is the pathway of IGF-1 regulating the secretion of COL-1 in fibroblasts.7.Lnc00839 can regulate IGF-1 expression and ultimately regulate the autophagy level of fibroblasts through AKT-m TOR-p70s6 k pathway,thereby regulating COL-1 secretion.Conclusions: 1.The expression of Lnc00839 in the vaginal wall of pelvic organ prolapse was decreased,and negatively correlated with the severity of pelvic organ prolapse.2.The low expression of IGF-1 and COL-1 may be related to the pathogenesis of pelvic organ prolapse.3.Lnc00839 can positively regulate the expression of IGF-1.Excessive autophagy and apoptosis of fibroblasts may be the pathophysiological basis of pelvic organ prolapse.4.Lnc00839 may interact with mi R-19-3p to target IGF-1,regulate the level of autophagy and apoptosis of fibroblasts,and increase the expression level of COL-1.5.Lnc00839 targets IGF-1 through mi R-19-3p,and then regulates the expression of COL-1 through AKT-m TOR-p70s6 k pathway. |
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