|
General Comment |
NCBI Summary:
This gene encodes a member of the Kunitz-type serine proteinase inhibitor family. The protein can inhibit a variety of serine proteases including factor VIIa/tissue factor, factor Xa, plasmin, trypsin, chymotryspin and plasma kallikrein. This gene has been identified as a tumor suppressor gene in several types of cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]
|
|
Comment |
Induction of Tissue Factor Pathway Inhibitor 2 by hCG regulates Periovulatory Gene Expression and Plasmin Activity. Puttabyatappa M et al. (2016) A key event during the process of ovulation is an increased proteolytic activity that aids in breakdown of the follicular wall to permit oocyte release. How the activity of these proteases is regulated is still not known. We hypothesize that Tissue Factor Pathway Inhibitor 2 (TFPI2), a matrix-associated Kunitz-type serine protease inhibitor, plays a role in regulating proteolytic activity during the periovulatory period as in other tissues. TFPI2 is secreted into the extracellular matrix (ECM) where it is postulated to regulate physiological ECM remodeling. The expression profile of TFPI2 during the periovulatory period was assessed utilizing a well-characterized human menstrual cycle model and a gonadotropin-primed rat model. Administration of an ovulatory dose of hCG increased TFPI2 expression dramatically in human and rat granulosa and theca cells. This increase in Tfpi2 expression in rat granulosa cells required hCG-mediated EGFR, PKA, ERK1/2, p38 MAPK and thrombin receptor PAR1-dependent cell signaling. A siRNA-mediated knockdown of TFPI2 in rat granulosa cells resulted in increased plasmin activity in the granulosa cell conditioned media. Knockdown of TFPI2 also reduced expression of multiple genes including Il6 and Areg. Overexpression of TFPI2 using an adenoviral vector partially restored the expression of Il6 and Areg in TFPI2 siRNA treated rat granulosa cells. These data support the hypothesis that TFPI2 is important for moderating plasmin activity and regulating granulosa cell gene expression during the periovulatory period. We therefore propose that through these actions, TFPI2 aids in the tissue remodeling taking place during follicular rupture and corpus luteum formation.//////////////////
|
|
Comment |
Differential expression of inflammation-related genes in the ovarian stroma and granulosa cells of PCOS women. Johanna Schmidt JS 2013 et al.
Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder. Ovarian changes in PCOS women are well characterised by ultrasound. However, the ovarian pathophysiology is not fully understood. The aim of this study was to characterise the expression, in both the central ovarian stroma and in granulosa cells (GC), of a number of genes, including several inflammation-related genes, which have been hypothesised to be involved in the pathophysiology of PCOS.Biopsies of the central ovarian stroma were obtained from PCOS women (Rotterdam criteria) and from normally ovulating women in follicular phase. Granulosa cells were retrieved from PCOS-women ornon-PCOS women, undergoing in vitro maturation (IVM). The expressions of 57 genes were analysed by quantitative-PCR using a Low-Density-Gene-Array. The main outcome measures were over-expression or under-expression of the specific genes.The results showed that in the central stroma of PCOS ovaries, five inflammation-related genes (CCL2, IL1R1, IL8, NOS2, TIMP1), the leukocyte marker CD45, the inflammation-related transcription factor RUNX2 and the growth factor AREG were under-expressed. The growth factor DUSP12 and the coagulation factor TFPI2 were over-expressed. In the GC of PCOS, all of the differentially expressed genes were over-expressed; the inflammation-related IL1B, IL8, LIF, NOS2 and PTGS2, the coagulation-related F3 and THBS1, the growth factors BMP6 and DUSP12, the permeability-related AQ3 and the growth-arrest-related GADD45A.In conclusion the results indicate major alterations in the local ovarian immune system of PCOS ovaries. This may have implications for the PCOS-related defects in the inflammation-like ovulatory process and for the susceptibility to acquire the inflammatory state of ovarian hyperstimulation syndrome.
/////////////////////////
in granulosa cells gene expression associated with increased oocyte competence in bovine. Nivet AL et al. One of the challenges in mammalian reproduction is to understand basic physiology of oocyte quality. It is believed that the follicle status is linked to developmental competence of the enclosed oocyte. To explore the link between follicles and competence in cows, a previous experiment from our laboratory has developed an ovarian stimulation protocol that increases and then decreases oocyte quality according to the timing of oocyte recovery post FSH withdrawal (coasting). Using such protocol, we have obtained the granulosa cells associated with oocytes of different qualities at selected times of coasting. Transcriptome analysis was done with Embryogene microarray slides and validation by real-time PCR. Results shows that the major changes in gene expression occurred from 20h to 44h of coasting, when oocyte quality rising. Secondly, among up-regulated genes (20h to 44h), 25%were extracellular molecules, highlighting potential granulosa signaling cascades. Principal component analysis identified 2 patterns: one resembling the competence profile and another associated with follicle growth and atresia. Additionally, 3 major functional changes were identified: 1) the end of follicle growth (BMPR1B, IGF2, RELN), involving interactions with the extracellular matrix (TFPI2); angiogenesis (NRP1), including early hypoxia, and potentially oxidative stress (GFPT2, TF, VNN1) and 2) apoptosis (KCNJ8) followed by 3) inflammation (ANKRD1). This unique window of analysis indicates a progressive hypoxia during coasting mixed with an increase of apoptosis and inflammation. Potential signaling pathways leading to competence have been identified and will require downstream testing. This preliminary analysis supports the potential role of the follicular differentiation in oocyte quality both during competence increase and decrease phases.
|