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2017 ; 40
(4
): 987-998
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Advanced glycation end products decrease collagen I levels in fibroblasts from
the vaginal wall of patients with POP via the RAGE, MAPK and NF-?B pathways
#MMPMID28849117
Chen YS
; Wang XJ
; Feng W
; Hua KQ
Int J Mol Med
2017[Oct]; 40
(4
): 987-998
PMID28849117
show ga
The present study was carried out to observe the impact of advanced glycation end
products (AGEs) on collagen I derived from vaginal fibroblasts in the context of
pelvic organ prolapse (POP), and explore the downstream effects on MAPK and
nuclear factor-?B (NF-?B) signaling. After treating primary cultured human
vaginal fibroblasts (HVFs) derived from POP and non-POP cases with AGEs, cell
counting was carried out by sulforhodamine B. The expression levels of
collagen I, receptor of advanced glycation end products (RAGE), matrix
metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1)
were detected by western blot analysis and PCR. RAGE, MAPK and NF-?B were
molecularly and pharmacologically-inhibited by siRNA, SB203580 and PDTC,
respectively, and downstream changes were detected by western blot analysis and
PCR. Inhibition of HVF proliferation by AGEs occurred more readily in POP
patients than that noted in the controls. After treatment with AGEs, collagen I
levels decreased and MMP-1 levels increased to a greater extent in the HVFs of
POP than that noted in the controls. During this same period, RAGE and TIMP-1
levels remained stable. Following treatment with AGEs and RAGE pathway inhibitors
by siRNA, SB203580 and PDTC, the impact induced by AGEs was diminished. The
inhibition of p-p38 MAPK alone was not able to block the promoting effect of AGEs
on the levels of NF-?B, which suggests that AGEs may function through other
pathways, as well as p-p38 MAPK. On the whole, this study demonstrated that AGEs
inhibited HVF proliferation in POP cases and decreased the expression of
collagen I through RAGE and/or p-p38 MAPK and NF-?B-p-p65 pathways. Our results
provide important insights into the collagen I metabolism in HVFs in POP.
|Aged
[MESH]
|Case-Control Studies
[MESH]
|Cell Proliferation/drug effects
[MESH]
|Collagen Type I/antagonists & inhibitors/*genetics/metabolism
[MESH]