Expression profiling of purified mouse gonadal somatic cells during the critical time window of sex determination reveals novel candidate genes for human sexual dysgenesis syndromes Beverdam A, et al./////Lipocalin2 enhances the matrix metalloproteinase-9 activity and invasion of extravillous trophoblasts under hypoxia. Kobara H 2013 et al.
OBJECTIVES
The invasion of extravillous trophoblasts (EVTs) to the decidua and spiral arteries in early pregnancy is a crucial step for a successful pregnancy; however, its mechanisms are not fully understood. Lipocalin2 (LCN2), a multifunctional secretory protein known as neutrophil gelatinase-associated lipocalin (NGAL), reportedly enhanced invasiveness via the activation of matrix metalloproteinase-9 (MMP-9) in several cancer cells. In this study, the expression and function of LCN2 in early placenta were analyzed.
METHODS
Early placental tissues between 7 and 10 weeks of gestation were obtained from normal pregnant women who underwent elective termination. The expression of LCN2 was examined using immunostaining and RT-PCR. EVTs isolated from these placental tissues and a choriocarcinoma cell line (JAR) were used to investigate the effects of LCN2 on proliferation, invasion potential, and MMP-9 activity under hypoxia using a WST-1 assay, Matrigel invasion assay, and gelatin gel zymography, respectively.
RESULTS
The immunohistochemical expression of LCN2 was observed in the cytoplasm of EVTs, cytotrophoblasts and the decidua, but not in syncytiotrophoblasts. The addition of recombinant LCN2 did not affect proliferation, but enhanced the invasiveness (500 ng/mL, p < 0.01) and MMP-9 activity of primary cultured EVTs and JAR in a dose-dependent manner. Silencing LCN2 using shRNA reduced the invasiveness (p < 0.01) and MMP-9 activity of JAR. In addition, the hypoxic condition (2% O2) increased LCN2 expression (p < 0.01), MMP-9 activity, and invasive ability (p < 0.01).
CONCLUSIONS
LCN2 was involved in the invasiveness of EVTs, especially under hypoxia, via increased MMP-9 activity.
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NCBI Summary:
This gene encodes a protein that belongs to the lipocalin family. Members of this family transport small hydrophobic molecules such as lipids, steroid hormones and retinoids. The protein encoded by this gene is a neutrophil gelatinase-associated lipocalin and plays a role in innate immunity by limiting bacterial growth as a result of sequestering iron-containing siderophores. The presence of this protein in blood and urine is an early biomarker of acute kidney injury. This protein is thought to be be involved in multiple cellular processes, including maintenance of skin homeostasis, and suppression of invasiveness and metastasis. Mice lacking this gene are more susceptible to bacterial infection than wild type mice. [provided by RefSeq, Sep 2015]
General function
Ligand
Comment
Cellular localization
Secreted
Comment
Serum lipocalin-2 as an insulin resistance marker in patients with polycystic ovary syndrome. Cakal E et al. (2011) Our aim was to investigate levels of lipocalin-2 and its relationship with metabolic factors in women with polycystic ovary syndrome (PCOS). In this cross-sectional study, two groups of women were studied: group 1 consisted of women with PCOS (no.=30), and group 2 consisted of control women with normal ovulatory function (no.=30). The circulating levels of free testosterone (T), DHEAS, glucose, insulin, triglycerides (TG), HDL, LDL and lipocalin were measured. Insulin resistance was assessed using the homeostasis model assessment (HOMA-IR). In order to determine a lipocalin value indicating insulin resistance, receiver operating characteristic (ROC) curves were established. Serum lipocalin was significantly higher in PCOS subjects (54.26 ± 15.58 vs 26.09 ± 7.47 ng/ml, p=0.0001).We found a close correlation between lipocalin and insulin, lipocalin and HOMA-IR, lipocalin and T, and lipocalin and DHEAS. A cut-off level of >39.54 ng/ml for serum lipocalin has a predictive value for insulin resistance of 81% sensitivity and 82.1% specificity. In our study, lipocalin-2 levels were found to be significantly higher in women with PCOS compared to body mass index-matched controls. Serum lipocalin-2 may prove to be a useful marker for insulin resistance in patients with PCOS.//////////////////
Ovarian function
Comment
The relationship between subclinical cardiovascular disease and lipocalin-2 levels in women with PCOS. Gencer M 2014 et al.
OBJECTIVE
In this study we aimed to investigate the relationship between lipocalin-2 (LCN2) levels and cardiovascular risk in patients with polycystic ovary syndrome (PCOS).
STUDY DESIGN
Fifty patients with PCOS and 44 healthy women as controls were enrolled in the study. Laboratory and echocardiographic examinations were performed between the second and fifth days of the menstrual cycle. Serum LCN2 levels were measured with an enzyme-linked immunosorbent assay (ELISA) method.
RESULTS
Serum LCN2 levels were significantly lower in PCOS patients (75.8 [51.4-131.2] ng/ml vs. 85.3 [56.7-138.5] ng/ml, p=0.038). Carotid intima-media thickness (CIMT) was increased in patients with PCOS compared to controls (0.61?0.13mm vs. 0.50?0.07mm, p=0.001). Aortic strain was lower in patients with PCOS. Aortic stiffness (?index) was significantly increased and distensibility was decreased in PCOS patients compared to control subjects. Serum LCN2 levels and the presence of PCOS were associated with CIMT in Spearman correlation analysis (p=0.05 and p<0.001) in all participants. There was no statistically significant relationship between LCN2 levels and CIMT in patients with PCOS (p=0.238).
CONCLUSION
In the present study, we found that LCN2 levels were low in women with PCOS. Although our patients with PCOS had elevated cardiac risk, there was no correlation between LCN2 levels and early findings of atherosclerosis.
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