IGF-1 regulates the growth of fibroblasts and extracellular matrix deposition in pelvic organ prolapse

Abstract

This study was carried out to observe the impact of insulin-like growth factor-1 (IGF-1) on human vaginal fibroblasts (HVFs) in the context of pelvic organ prolapse (POP) and to explore its effects on mitogen-activated protein kinases (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. First, it was found that IGF-1 expression reduced in the vaginal wall tissues derived from POP compared to that in non-POP cases. Then the role of IGF-1 was explored in HVFs and thiazolyl blue tetrazolium bromide (MTT) and flow cytometry were used to detect cell viability and cell apoptosis. Western blot assay and quantitative real-time polymerase chain reaction were used to detect the protein and mRNA expression. The results showed that knockdown of IGF-1 inhibited the cell viability of HVFs, promoted the cell apoptosis of HVFs, and decreased the expression of types I and III collagen in HVFs, which was through inhibiting the expression of IGF-1 receptor and MAPK/NF-κB pathways. However, IGF-1 plasmid had the opposite effects on HVFs. In conclusion, our results showed that IGF-1 could activate MAPK and NF-κB pathways, thereby enhancing collagen metabolism and the growth of vaginal wall fibroblasts then to inhibit POP development.

FZD3 regulates the viability, apoptosis, and extracellular matrix degradation of vaginal wall fibroblasts in pelvic organ prolapse via the Wnt signaling pathway

“…[23,24] Moreover, the growth and apoptosis of fibroblasts are associated with POP. [25,26] Herein, VWFs were isolated from the vaginal wall tissues of patients with POP and non-POP. We found FZDs are regulators of cell phenotype that are involved in gynecological diseases, such as ovarian cancer, cervical cancer, and polycystic ovary syndrome.…”

“…[ 23,24 ] Moreover, the growth and apoptosis of fibroblasts are associated with POP. [ 25,26 ] Herein, VWFs were isolated from the vaginal wall tissues of patients with POP and non‐POP. We found VWFs are spindly.…”

Potential molecular targets for intervention in pelvic organ prolapse

“…IGF-1 belongs to the insulin-like growth factor family, which includes insulin-like polypeptides mainly synthesized by the liver. IGF-1 can regulate ECM metabolism and various biological processes, such as cell proliferation, differentiation, and apoptosis ( 40 , 41 ). One study ( 40 ) have shown that IGF-1 levels in vaginal wall tissues were lower in patients with POP than in non-POP controls, and it induced the proliferation of vaginal wall fibroblasts, activated mitogen-activated protein kinase (MAPK) and nuclear factor-κ-gene binding (NF-κB) pathways, promoted the metabolism of type I and III collagen another study ( 42 ) reported that IGF-1 can be used as an inhibitor of apoptosis and it may also stimulate fibroblasts to release ECM molecules, such as polysaccharides and proteins.…”

The Role of IGF/IGF-IR-Signaling and Extracellular Matrix Effectors in Bone Sarcoma Pathogenesis

“…Matrix molecules participate in different signaling pathways and finally control cellular behavior [118]. Their synergistic action with IGF/IGF-IR signaling pathway is involved in cancer's pathogenesis [119][120][121][122]. The interactions are perpetrated in two directions: (i) IGF/IGF-IR regulates sarcoma matrix effector synthesis, structure/organization, and downstream functions; and (ii) sarcoma matrix effectors modulate IGF/IGF-IR pathway restricted signaling.…”