title: Relationship of advanced glycation end products and their receptor to pelvic organ prolapse.
abstract: OBJECTIVE
  The aims of this study are to detect levels of AGEs and RAGE and SNPs for RAGE in vaginal tissues of women with POP and rats in a repair location, and to explore the relationship between AGEs-RAGE pathway and POP.
  
  
  METHODS
  This study involved human vaginal tissues in fornix from 44 women with POP and 46 women without POP who were assigned to pelvic floor reconstruction or LAVH. The proteins of AGEs, collagen I, and RAGE were detected by immunohistochemistry and Western blot with appropriate primary antibodies. The entire RAGE gene of 24 women with POP and 25 controls were sequenced, and SNPs within were detected. Then, sixty 8-week-old female Sprague-Dawley rats subjected to abdominal defect were divided into three surgical pelvic floor reconstruction repair groups (n=20/group): A, repair with non-absorable prolene mesh; B, repair with absorbable SIS mesh; and C, a no repair control group. 3, 9, 15, and 21 months after operation, rats were sacrificed and the expression of AGEs, RAGE and collagen I in the tissues of repair location were detected in the various experimental groups. Statistical analysis included comparison of means (Student's t-test) and proportions (Chi-square test or Fisher test).
  
  
  RESULTS
  By both immunohistochemistry and Western blot, patients with POP showed higher protein expression of AGEs of POP than controls (P<0.05). In contrast, the expression of collagen I was lower in POP patients than in the control group (P<0.05). No differences in the expression of RAGE between the POP patients and controls were observed (P>0.05). In POP patients, the expression of collagen I decreased particularly in patients≥60 years old (P<0.05), but there were no different in the expression of AGEs and RAGE dependent on age (P>0.05). RAGE gene sequence variance analysis identified 18 variable loci, but only two of these were potential SNPs: rs184003 (1806), rs55640627 (2346) (P<0.05). Both rs184003 and rs55640627 are both intronic variants, indicating that they may not influence the structure of RAGE. In rat surgical repair model, group B showed a greater extent of abdominal prolapse than groups A and C (P<0.05). Consistent with this, the expression of AGEs in group B was higher than groups A and C (P<0.05), and collagen I in group B was lower than the two others, further supporting our notion that AGEs are inversely related to type I collagen content.
  
  
  CONCLUSIONS
  In summary, this study demonstrates that AGEs and RAGE might play important roles in the physiopathology of POP. Further studies are required to explore mechanisms of how AGEs-RAGE pathway may contribute to tissue degeneration and fragility in POP.
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University Shanghai 200011, China.
authors.forename: Yisong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University Shanghai 200011, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University Shanghai 200011, China.
authors.forename: Changdong
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University Shanghai 200011, China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai 200011, China.
authors.forename: Keqin
authors.initials: K
authors.lastname: Hua
mesh_terms: D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D017773:Pelvic Floor / Q000601:surgery; D056887:Pelvic Organ Prolapse / Q000175:diagnosis / Q000378:metabolism* / Q000601:surgery; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D014621:Vagina / Q000378:metabolism* / Q000601:surgery
chemical_list: C000593871:AGER protein, human; C000593874:Ager protein, rat; D024042:Collagen Type I; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products
keywords: AGEs; POP; RAGE; collagen I; gene sequence