scholarly journals ITGAV (alpha v integrins) bind SPP1 (osteopontin) to support trophoblast cell adhesion

Reproduction ◽  
2017 ◽  
Vol 153 (5) ◽  
pp. 695-706 ◽  
Author(s):  
James W Frank ◽  
Heewon Seo ◽  
Robert C Burghardt ◽  
Kayla J Bayless ◽  
Greg A Johnson
Keyword(s):  
Cell Adhesion ◽  
Mrna Expression ◽  
Focal Adhesions ◽  
Trophoblast Cell ◽  
Luminal Epithelium ◽  
Mechanical Forces ◽  
Integrin Receptors ◽  
Spatial Expression ◽  
Secreted Phosphoprotein 1

Attachment of the conceptus trophoblast (Tr) to the uterine luminal epithelium (LE) is critical for successful implantation. This study determined whether alpha v (av) integrins (ITGAV) directly mediate porcine trophoblast cell adhesion to secreted phosphoprotein 1 (SPP1, also known as osteopontin (OPN)) and examined the temporal/spatial expression of ITGAV, beta 3 (b3, ITGB3) and beta 6 (b6, ITGB6) integrin subunits, and SPP1, at the uterine–placental interface of pigs. Knockdown ofITGAVin porcine Tr (pTr2) cells by siRNA reduced pTr2 attachment to SPP1.In situhybridization confirmed the presence ofITGAV,ITGB3andITGB6mRNAs in uterine LE and conceptus Tr between Days 9 and 60 of gestation, with no change in the magnitude of expression over the course of pregnancy. Exogenous E2 or P4 did not affectITGAV,ITGB3andITGB6mRNA expression in the uteri of ovariectomized gilts. Immunofluorescence identified ITGAV, ITGB3 and SPP1 proteins in large aggregates at the uterine LE-placental Tr/chorion interface on Day 25, but aggregates were no longer observed by Day 50 of gestation. These results are the first to directly demonstrate that pTr2 cells engage ITGAV-containing integrin receptors to adhere to SPP1 and suggest that mechanical forces generated by tethering elongating conceptuses to uterine LE leads to assembly of focal adhesions containing ITGAV and SPP1; however, as placentation progresses, subsequent folding/interdigitation at the uterine–placental interface disperses mechanical forces resulting in the loss of focal adhesions.

Influence of cytoskeletal structure and mechanics on epithelial cell injury during cyclic airway reopening

2009 ◽  
Vol 297 (5) ◽  
pp. L881-L891 ◽  
Author(s):  
H. C. Yalcin ◽  
K. M. Hallow ◽  
J. Wang ◽  
M. T. Wei ◽  
H. D. Ou-Yang ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Epithelial Cell ◽  
Cell Viability ◽  
Cell Injury ◽  
Focal Adhesions ◽  
Viscous Damping ◽  
Mechanical Forces ◽  
Damping Properties ◽  
Airway Reopening ◽  
Cytoskeletal Structure

Although patients with acute respiratory distress syndrome require mechanical ventilation, these ventilators often exacerbate the existing lung injury. For example, the cyclic closure and reopening of fluid-filled airways during ventilation can cause epithelial cell (EpC) necrosis and barrier disruption. Although much work has focused on minimizing the injurious mechanical forces generated during ventilation, an alternative approach is to make the EpC less susceptible to injury by altering the cell's intrinsic biomechanical/biostructural properties. In this study, we hypothesized that alterations in cytoskeletal structure and mechanics can be used to reduce the cell's susceptibility to injury during airway reopening. EpC were treated with jasplakinolide to stabilize actin filaments or latrunculin A to depolymerize actin and then exposed to cyclic airway reopening conditions at room temperature using a previously developed in vitro cell culture model. Actin stabilization did not affect cell viability but significantly improved cell adhesion primarily due to the development of more numerous focal adhesions. Surprisingly, actin depolymerization significantly improved both cell viability and cell adhesion but weakened focal adhesions. Optical tweezer based measurements of the EpC's micromechanical properties indicate that although latrunculin-treated cells are softer, they also have increased viscous damping properties. To further investigate the effect of “fluidization” on cell injury, experiments were also conducted at 37°C. Although cells held at 37°C exhibited no changes in cytoskeletal structure, they did exhibit increased viscous damping properties and improved cell viability. We conclude that fluidization of the actin cytoskeleton makes the EpC less susceptible to the injurious mechanical forces generated during cyclic airway reopening.

scholarly journals Dual effect of transforming growth factor β1 on cell adhesion and invasion in human placenta trophoblast cells

Reproduction ◽  
2006 ◽  
Vol 132 (2) ◽  
pp. 333-341 ◽  
Author(s):  
Mei-rong Zhao ◽  
Wei Qiu ◽  
Yu-xia Li ◽  
Zhi-bin Zhang ◽  
Dong Li ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Growth Factor ◽  
Mrna Expression ◽  
Cell Invasion ◽  
Human Placenta ◽  
Transforming Growth Factor ◽  
Trophoblast Cell ◽  
Rt Pcr ◽  
Human Trophoblast ◽  
Adhesion And Invasion

Transforming growth factor β (TGFβ) has been shown to be a multifunctional cytokine required for embryonic development and regulation of trophoblast cell behaviors. In the present study, a non-transformed cell-line representative of normal human trophoblast (NPC) was used to examine the effect of TGFβ1 on trophoblast cell adhesion and invasion. In vitro assay showed that TGFβ1 could significantly promote intercellular adhesion, while inhibiting cell invasion across the collagen I-coated filter. Reverse transcription (RT)-PCR and gelatin zymography demonstrated that TGFβ1 evidently repressed the mRNA expression and proenzyme production of matrix metalloproteinase (MMP)-9, but exerted no effect on mRNA expression and secretion of MMP-2. On the other hand, both the mRNA and protein expression of epithelial-cadherin and β-catenin were obviously upregulated by TGFβ1 in dose-dependent fashion, as revealed by RT-PCR and western-blot analysis. What is more, one of the critical TGFβ signaling molecules – Smad2 was notably phosphorylated in TGFβ1-treated NPC cells. The data indicates that cell invasion and adhesion are coordinated processes in human trophoblasts and that there exists paracrine regulation on adhesion molecules and invasion-associated enzymes in human placenta.

scholarly journals Secreted phosphoprotein 1 (osteopontin) is expressed by stromal macrophages in cyclic and pregnant endometrium of mice, but is induced by estrogen in luminal epithelium during conceptus attachment for implantation

Reproduction ◽  
2006 ◽  
Vol 132 (6) ◽  
pp. 919-929 ◽  
Author(s):  
Frankie J White ◽  
Robert C Burghardt ◽  
Jianbo Hu ◽  
Margaret M Joyce ◽  
Thomas E Spencer ◽  
...  
Keyword(s):  
Estrous Cycle ◽  
Immune Cells ◽  
Luminal Epithelium ◽  
Apical Surface ◽  
Wild Type ◽  
Mouse Uterus ◽  
Ovariectomized Mice ◽  
Vaginal Plug ◽  
Secreted Phosphoprotein 1

Secreted phosphoprotein 1 (SPP1, osteopontin) is the most highly upregulated extracellular matrix/adhesion molecule/cytokine in the receptive phase human uterus, and Spp1 null mice manifest decreased pregnancy rates during mid-gestation as compared with wild-type counterparts. We hypothesize that Spp1 is required for proliferation, migration, survival, adhesion, and remodeling of cells at the conceptus–maternal interface. Our objective was to define the temporal/spatial distribution and steroid regulation of Spp1 in mouse uterus during estrous cycle and early gestation.In situhybridization localizedSpp1to luminal epithelium (LE) and immune cells. LE expression was prominent at proestrus, decreased by estrus, and was nearly undetectable at diestrus. During pregnancy,Spp1mRNA was not detected in LE until day 4.5 (day 1 = vaginal plug).Spp1-expressing immune cells were scattered within the endometrial stroma throughout the estrous cycle and early pregnancy. Immunoreactive Spp1 was prominent at the apical LE surface by day 4.5 of pregnancy and Spp1 protein was also co-localized with subsets of CD45-positive (leukocytes) and F4/80-positive (macrophages) cells. In ovariectomized mice, estrogen, but not progesterone, inducedSpp1mRNA, whereas estrogen plus progesterone did not induceSpp1in LE. These results establish that estrogen regulates Spp1 in mouse LE and are the first to identify macrophages that produce Spp1 within the peri-implantation endometrium of any species. We suggest that Spp1 at the apical surface of LE provides a mechanism to bridge conceptus to LE during implantation, and that Spp1-positive macrophages within the stroma may be involved in uterine remodeling for conceptus invasion.

scholarly journals Integrins: An Important Link between Angiogenesis, Inflammation and Eye Diseases

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1703
Author(s):  
Małgorzata Mrugacz ◽  
Anna Bryl ◽  
Mariusz Falkowski ◽  
Katarzyna Zorena
Keyword(s):  
Cell Adhesion ◽  
Tissue Repair ◽  
Normal Development ◽  
Cell Attachment ◽  
Biological Activities ◽  
Integrin Receptors ◽  
Cytokine Activation ◽  
Eye Disorders ◽  
Membrane Bound ◽  
Cell To Cell Adhesion

Integrins belong to a group of cell adhesion molecules (CAMs) which is a large group of membrane-bound proteins. They are responsible for cell attachment to the extracellular matrix (ECM) and signal transduction from the ECM to the cells. Integrins take part in many other biological activities, such as extravasation, cell-to-cell adhesion, migration, cytokine activation and release, and act as receptors for some viruses, including severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). They play a pivotal role in cell proliferation, migration, apoptosis, tissue repair and are involved in the processes that are crucial to infection, inflammation and angiogenesis. Integrins have an important part in normal development and tissue homeostasis, and also in the development of pathological processes in the eye. This review presents the available evidence from human and animal research into integrin structure, classification, function and their role in inflammation, infection and angiogenesis in ocular diseases. Integrin receptors and ligands are clinically interesting and may be promising as new therapeutic targets in the treatment of some eye disorders.

scholarly journals MAML1: a coregulator that alters endometrial epithelial cell adhesive capacity

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Sadaf Zafir ◽  
Wei Zhou ◽  
Ellen Menkhorst ◽  
Leilani Santos ◽  
Evdokia Dimitriadis
Keyword(s):  
Notch Signaling ◽  
Cell Line ◽  
Notch Signaling Pathway ◽  
Endometrial Receptivity ◽  
Trophoblast Cell ◽  
Luminal Epithelium ◽  
Secretory Phase ◽  
Ishikawa Cells ◽  
Trophoblast Cell Line ◽  
Adhesive Capacity

Abstract Background Abnormalities in endometrial receptivity has been identified as a major barrier to successful embryo implantation. Endometrial receptivity refers to the conformational and biochemical changes occurring in the endometrial epithelial layer which make it adhesive and receptive to blastocyst attachment. This takes place during the mid-secretory phase of woman’s menstrual cycle and is a result of a delicate interplay between numerous hormones, cytokines and other factors. Outside of this window, the endometrium is refractory to an implanting blastocyst. It has been shown that Notch ligands and receptors are dysregulated in the endometrium of infertile women. Mastermind Like Transcriptional Coactivator 1 (MAML1) is a known coactivator of the Notch signaling pathway. This study aimed to determine the role of MAML1 in regulating endometrial receptivity. Methods The expression and localization of MAML1 in the fertile human endometrium (non-receptive proliferative phase versus receptive mid-secretory phase) were determined by immunohistochemistry. Ishikawa cells were used as an endometrial epithelial model to investigate the functional consequences of MAML1 knockdown on endometrial adhesive capacity to HTR8/SVneo (trophoblast cell line) spheroids. After MAML1 knockdown in Ishikawa cells, the expression of endometrial receptivity markers and Notch dependent and independent pathway members were assessed by qPCR. Two-tailed unpaired or paired student’s t-test were used for statistical analysis with a significance threshold of P < 0.05. Results MAML1 was localized in the luminal epithelium, glandular epithelium and stroma of human endometrium and the increased expression identified in the mid-secretory phase was restricted only to the luminal epithelium (P < 0.05). Functional analysis using Ishikawa cells demonstrated that knockdown of MAML1 significantly reduced epithelial adhesive capacity (P < 0.01) to HTR8/SVneo (trophoblast cell line) spheroids compared to control. MAML1 knockdown significantly affected the expression of classical receptivity markers (SPP1, DPP4) and this response was not directly via hormone receptors. The expression level of Hippo pathway target Ankyrin repeat domain-containing protein 1 (ANKRD1) was also affected after MAML1 knockdown in Ishikawa cells. Conclusion Our data strongly suggest that MAML1 is involved in regulating the endometrial adhesive capacity and may facilitate embryo attachment, either directly or indirectly through the Notch signaling pathway.

Expression of transforming growth factor alpha during development

1988 ◽  
Vol 66 (8) ◽  
pp. 1113-1121 ◽  
Author(s):  
V. K. M. Han ◽  
A. J. D'Ercole ◽  
D. C. Lee
Keyword(s):  
In Situ Hybridization ◽  
Growth Factor ◽  
Mrna Expression ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Alpha ◽  
Egf Receptors ◽  
Hybridization Histochemistry ◽  
In Situ Hybridization Histochemistry ◽  
Factor Alpha

Transforming growth factors (TGFs) are polypeptides that are produced by transformed and tumour cells, and that can confer phenotypic properties associated with transformation on normal cells in culture. One of these growth-regulating molecules, transforming growth factor alpha (TGF-α), is a 50 amino acid polypeptide that is related to epidermal growth factor (EGF) and binds to the EGF receptor. Previous studies have shown that TGF-α is expressed during rodent embryogenesis between 7 and 14 days gestation. To investigate the cellular sites of TGF-α mRNA expression during development, we have performed Northern analyses and in situ hybridization histochemistry on the conceptus and maternal tissues at various gestational ages. Contrary to previous reports, both Northern analyses and in situ hybridization histochemistry indicate that TGF-α mRNA is predominantly expressed in the maternal decidua and not in the embryo. Decidual expression is induced following implantation, peaks at day 8, and declines through day 15 when the decidua is being resorbed. In situ hybridization revealed that expression of TGF-α mRNA is highest in the region of decidua adjacent to the embryo and is low or nondetectable in the uterus, placenta, and embryo. In addition, we could not detect TGF-α mRNA expression in other maternal tissues, indicating that the induction of TGF-α transcripts in the decidua is tissue specific, and not a pleiotropic response to changes in hormonal milieu that occur during pregnancy. The developmentally regulated expression of TGF-α mRNA in the decidua, together with the presence of EGF receptors in this tissue, suggests that this peptide may stimulate mitosis and angiogenesis locally by an autocrine mechanism. Because EGF receptors are also present in the embryo and placenta, TGF-α may act on these tissues by a paracrine or endocrine mechanism.

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