scholarly journals The role of tight junction proteins in ovarian follicular development and ovarian cancer

Reproduction ◽  
2018 ◽  
Vol 155 (4) ◽  
pp. R183-R198 ◽  
Author(s):  
Lingna Zhang ◽  
Tao Feng ◽  
Leon J Spicer
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor ◽  
Tight Junction ◽  
Protein Structures ◽  
Follicular Development ◽  
Current Evidence ◽  
Serum Factors ◽  
Cell Functions ◽  
Junction Protein ◽  
Ovarian Follicular Development

Tight junctions (TJ) are protein structures that control the transport of water, ions and macromolecules across cell layers. Functions of the transmembrane TJ protein, occluding (OCLN) and the cytoplasmic TJ proteins, tight junction protein 1 (TJP1; also known as zona occludens protein-1), cingulin (CGN) and claudins (CLDN) are reviewed, and current evidence of their role in the ovarian function is reviewed. Abundance ofOCLN,CLDNsandTJP1mRNA changed during follicular growth.In vitrotreatment with various growth factors known to affect ovarian folliculogenesis indicated thatCGN,OCLNandTJP1are hormonally regulated. The summarized studies indicate that expression of TJ proteins (i.e.,OCLN,CLDN,TJP1andCGN) changes with follicle size in a variety of vertebrate species but whether these changes in TJ proteins are increased or decreased depends on species and cell type. Evidence indicates that autocrine, paracrine and endocrine regulators, such as fibroblast growth factor-9, epidermal growth factor, androgens, tumor necrosis factor-α and glucocorticoids may modulate these TJ proteins. Additional evidence presented indicates that TJ proteins may be involved in ovarian cancer development in addition to normal follicular and luteal development. A model is proposed suggesting that hormonal downregulation of TJ proteins during ovarian follicular development could reduce barrier function (i.e., selective permeability of molecules between theca and granulosa cells) and allow for an increase in the volume of follicular fluid as well as allow additional serum factors into the follicle that may directly impact granulosa cell functions.

scholarly journals Transcription profile of the insulin-like growth factor signaling pathway during human ovarian follicular development

2019 ◽  
Vol 36 (5) ◽  
pp. 889-903 ◽  
Author(s):  
Jane Alrø Bøtkjær ◽  
Susanne Elisabeth Pors ◽  
Tonny Studsgaard Petersen ◽  
Stine Gry Kristensen ◽  
Janni Vikkelsø Jeppesen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Signaling Pathway ◽  
Follicular Development ◽  
Growth Factor Signaling ◽  
Insulin Like Growth Factor ◽  
Transcription Profile ◽  
Ovarian Follicular Development ◽  
Growth Factor Signaling Pathway

257 Awardee Talk: Pursuit of Novel Factors that Regulate Ovarian Follicular Function

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 138-139
Author(s):  
Leon J Spicer
Keyword(s):  
Growth Factor ◽  
Vascular Dysfunction ◽  
Follicular Development ◽  
Research Knowledge ◽  
Estrous Synchronization ◽  
Affymetrix Microarrays ◽  
Ovarian Follicular Development ◽  
Transcription Factor E2f ◽  
New Treatments ◽  
Endothelial Growth Factor

Abstract As follicles grow, theca cells (TC) and granulosa cells (GC) must proliferate with minimal differentiation while thecal vascularization increases so that follicles do not prematurely ovulate or luteinize before the oocyte is fully mature. In the early 2000s we used Affymetrix microarrays to discover several unique genes involved in ovarian follicular development. Thrombospondin and fibroblast growth factor (FGF) 2 receptor genes were stimulated by IGF1 in porcine GC. We compared GC gene expression in bovine cystic versus normal follicles and discovered several novel genes including Indian hedgehog protein (IHH), FGF9, brain ribonuclease (BRB), and G protein-coupled receptor 34 (GPR34), leading to identification of roles for these proteins in ovarian follicular development. During the past 10 years, follow-up TC microarray and mechanistic studies have identified FGF9 control of cell cycle proteins, tight junction proteins, and microRNA 221 (MIR221), and that the mitogenic and steroidogenic responses to the major trophic hormones of the ovary (including IGF1, LH and FSH) are altered by overexpression of MIR221 in GC. In addition, we discovered that: 1) FGF9 stimulates GC and TC mitosis while inhibiting steroidogenesis; 2) FGF9 induces E2 transcription factor (E2F)-1, E2F-8 and cyclin D1 (CCND1), and that both IGF1 and vascular endothelial growth factor-A (VEGFA) synergize with FGF9 to further induce E2F8 and CCND1 mRNA; 3) FGF9 induces the nuclear protein UHRF1; and 4) an E2F inhibitor blocks the stimulatory and inhibitory effects of FGF9 on GC proliferation and steroidogenesis, respectively, and down-regulates UHRF1 mRNA and up-regulates VEGFA mRNA. Thus, aberrant production of FGF9 and the factors it induces/inhibits may lead to vascular dysfunction and ovarian disorders such as ovarian cysts. With additional research, knowledge about these newly identified factors may be used to help the livestock industry improve reproductive efficiency via new treatments for estrous synchronization, superovulation and cystic ovaries.

Epidermal growth factor induces tyrosine phosphorylation and reorganization of the tight junction protein ZO-1 in A431 cells

1995 ◽  
Vol 108 (4) ◽  
pp. 1735-1742 ◽  
Author(s):  
C.M. Van Itallie ◽  
M.S. Balda ◽  
J.M. Anderson
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tight Junction ◽  
Tyrosine Phosphorylation ◽  
Intercellular Junctions ◽  
Cytochalasin D ◽  
Tight Junction Protein ◽  
A431 Cells ◽  
Junction Protein ◽  
Epidermal Growth

Addition of epidermal growth factor (EGF) to A431 human epidermal carcinoma cells results in actin reorganization and phosphorylation of several cytoskeletal proteins. In the present study, we found that EGF treatment of this cell line also results in the redistribution and tyrosine phosphorylation of ZO-1. In normal polarized epithelial cells, ZO-1 is restricted to the cytoplasmic surface of the most apical of the intercellular junctions, the tight junction. In contrast, ZO-1 in the majority of unstimulated A431 cells in small subconfluent islands colocalizes with actin along the lateral cell membranes and in rare microspikes and membrane ruffles. Exposure to EGF results in a transient redistribution of actin into an apically positioned ring. ZO-1 becomes highly focused at apical sites of cell contact and co-localizes with the newly formed band of perijunctional actin. Coincidently, ZO-1 and another tight junction protein, ZO-2, become transiently phosphorylated on tyrosine residues, as determined by anti-phosphotyrosine immunoblotting. Pre-treatment of A431 cells with cytochalasin D, which disrupts normal microfilament organization, does not affect EGF-dependent phosphorylation of the EGF receptor. However, cytochalasin D pretreatment blocks both the EGF-induced ZO-1 rearrangement and tyrosine phosphorylation, suggesting that these responses are dependent on an intact actin microfilament system. We speculate that the transient tyrosine phosphorylation of ZO-1 in response to EGF treatment may be involved in remodeling of intercellular junctions in A431 cells.

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