Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0033377 (
prolapse
)
11,717
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
It was hypothesized that the processes contributing to pelvic organ
prolapse
(
POP
) may be identified by transcriptional profiling of pelvic connective tissue in conjunction with light microscopy. In order to test this, we performed a frequency-matched case-control study of women undergoing hysterectomy for
POP
and controls. Total RNA, extracted from uterosacral and round ligament samples used to generate labeled cRNA, was hybridized to microarrays and analyzed for the expression of 32 878 genes. Significance Analysis of Microarrays (Stanford University, CA, USA) identified differentially expressed genes used for ontoanalysis. Quantitative PCR (qPCR) confirmed results. Light microscopy confirmed the tissue type and assessed inflammatory infiltration. The analysis of 34 arrays revealed 249 differentially expressed genes with fold changes (FC) larger than 1.5 and false discovery rates < or =5.2%. Immunity and defense was the most significant biological process differentially expressed in
POP
. qPCR confirmed the elevated steady-state mRNA levels for four genes:
interleukin-6
(FC 9.8), thrombospondin 1 (FC 3.5) and prostaglandin-endoperoxide synthase 2 (FC 2.4) and activating transcription factor 3 (FC 2.6). Light microscopy showed all the samples were composed of fibromuscular connective tissue with no inflammatory infiltrates. In conclusion, genes enriched for 'immunity and defense' contribute to
POP
independent of inflammatory infiltrates.
...
PMID:Gene expression profile in pelvic organ prolapse. 1905 8
BACKGROUND Pelvic organ
prolapse
(
POP
) is due to age-related atrophy and the weakening of the tissues of the pelvic floor, with degradation of collagen and extracellular matrix (ECM) by metalloproteinases (MMPs). This study aimed to investigates the role of the age-related enzyme klotho, encoded by the KL gene, in cultured fibroblasts obtained from patients with
POP
and the levels of reactive oxygen species (ROS),
interleukin-6
(
IL-6
), and MMPs. MATERIAL AND METHODS Pelvic floor fibroblasts were obtained from connective tissue from three patients with
POP
and three normal subjects. Cell proliferation and ROS production were measured using a cell counting kit-8 (CCK-8) assay and flow cytometry. Levels of
interleukin-6
(
IL-6
), klotho, metalloproteinase-1 (MMP-1), MMP-3, extracellular signal-regulated kinases 1/2 (ERK1/2), and p-ERK1/2 were measured by enzyme-linked immunoassay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot. RESULTS In cultured pelvic floor fibroblasts from patients with
POP
, the expression of klotho protein and klotho mRNA were significantly down-regulated in fibroblasts from patients with
POP
compared with normal fibroblasts. Klotho supplementation in cultured fibroblasts for patients with
POP
included increased cell growth, reduced expression of ROS reduction, and reduced the secretion of
IL-6
. Using qRT-PCR and Western blot, klotho supplementation of fibroblasts from patients with
POP
increased cell growth and reduced the levels of
IL-6
and ROS in a dose-dependent way. CONCLUSIONS Klotho protein reduced the expression of MMP-1 and MMP-3 in fibroblasts from patients with
POP
by down-regulating the phosphorylation of ERK1/2.
...
PMID:Klotho Protein Reduced the Expression of Matrix Metalloproteinase-1 (MMP-1) and Matrix Metalloproteinase-3 (MMP-3) in Fibroblasts from Patients with Pelvic Organ Prolapse (POP) by Down-Regulating the Phosphorylation of ERK1/2. 3111 9
