Chondrocytes Are Regulated by Cellular Adhesion Through CD44 and Hyaluronic Acid Pathway

Facioscapulohumeral muscular dystrophy (FSHD) is linked to epigenetic derepression of the germline/embryonic transcription factor DUX4 in skeletal muscle. However, the etiology of muscle pathology is not fully understood, as DUX4 misexpression is not tightly correlated with disease severity. Using a DUX4-inducible cell model, we show that multiple DUX4-induced molecular pathologies that have been observed in patient-derived disease models are mediated by the signaling molecule hyaluronic acid (HA), which accumulates following DUX4 induction. These pathologies include formation of RNA granules, FUS aggregation, DNA damage, caspase activation, and cell death. We also observe previously unidentified pathologies including mislocalization of mitochondria and the DUX4- and HA-binding protein C1QBP. These pathologies are prevented by 4-methylumbelliferone, an inhibitor of HA biosynthesis. Critically, 4-methylumbelliferone does not disrupt DUX4-C1QBP binding and has only a limited effect on DUX4 transcriptional activity, establishing that HA signaling has a central function in pathology and is a target for FSHD therapeutics.

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Facile and Efficient Anti-Fouling Surface Construction on Poly(dimethylsiloxane) via Mussel-Inspired Chemistry

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.749.344 ◽

2013 ◽

Vol 749 ◽

pp. 344-349 ◽

Cited By ~ 1

Author(s):

Quan Kui Lin ◽

Xiao Jie Huang ◽

Jun Mei Tang ◽

Hao Chen

Keyword(s):

Hyaluronic Acid ◽

Thiol Group ◽

Cellular Adhesion ◽

Intraocular Lenses ◽

Acid Modification ◽

Pdms Surface ◽

In Vitro Adhesion ◽

Adhesive Proteins ◽

Surface Construction

Poly (dimethylsiloxane) (PDMS) silicones have found many applications in biomedical devices, such as catheters and intraocular lenses. But their hydrophobicity makes the possibility of the unexpected bioadhesion. In this paper, we reported a facile and efficient anti-fouling surface modification method on PDMS via self-polymerization of dopamine and the followed hyaluronic acid immobilization. Dopamine, commonly used as a neurotransmitter, is also a small molecule mimic of the adhesive proteins of mussels. Self-polymerization of dopamine can produce a thin polydopamine (PDA) layer on PDMS surface. Subsequently, thiol group functionalized hyaluronic acid (denoted as HA-SH) was immobilized covalently onto the resultant surface by the coupling between thiol group and reactive polydopamine layer. Then, the in vitro adhesion behaviors of the lens epithelial cells (LECs) and macrophage were investigated for evalution the anti-fouling effect of the hyaluronic acid modified PDMS surface. The results indicated that the cellular adhesion on PDMS were greatly decreased after hyaluronic acid modification, which suggested the potential application of such hyaluronic acid modified PDMS in biomedical applications.

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HYALURONIC ACID PATHWAY EXPRESSION IN ESTROGEN-PROGESTERONE TREATMENT AND PROGESTERONE ONLY TREATMENT OF ENDOMETRIOSIS

Fertility and Sterility ◽

10.1016/j.fertnstert.2021.07.569 ◽

2021 ◽

Vol 116 (3) ◽

pp. e208

Author(s):

Kathryn M. Goldrick ◽

Jennifer F. Knudtson ◽

Robert S. Schenken ◽

Mubeen Sultana ◽

Randal D. Robinson ◽

...

Keyword(s):

Hyaluronic Acid ◽

Progesterone Treatment ◽

Pathway Expression ◽

Acid Pathway

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O17: HYALURONIC ACID DEPENDENT ADHESION IN COLORECTAL CANCER PERITONEAL METASTASIS

British Journal of Surgery ◽

10.1093/bjs/znab117.017 ◽

2021 ◽

Vol 108 (Supplement_1) ◽

Author(s):

F Soliman ◽

L Ye ◽

W Jiang ◽

R Hargest

Keyword(s):

Colorectal Cancer ◽

Hyaluronic Acid ◽

Adhesion Molecules ◽

Peritoneal Metastasis ◽

Cellular Adhesion ◽

Adverse Outcomes ◽

The Body ◽

Receptor Interaction

Abstract Introduction Peritoneal Metastasis (PM) in Colorectal Cancer (CRC) undoubtedly remains a challenge to treat and often portends a poor prognosis for patients. Hyaluronic acid (HA) is found throughout the body, including coating of the peritoneum. Interaction of HA with HA-dependent adhesion molecules can facilitate cell adhesion within the peritoneum. HA may play a role in spread of PM in CRC in association with known HA-receptor molecules CD44, RHAMM and ICAM-1. Method Expression of HA-dependent and HA-independent adhesion molecules were examined in CRC using tissue microarray datasets and matched to clinicopathological data. In-vitro peritoneal modelling assessed cellular adhesion when treated with a competitive HA-inhibitor (HAi) or excess exogenous HA. An in-vivo Xenograft peritoneal model, using CD1 nude mice injected with CRC cells, were treated with either HAi or excess exogenous HA and compared to a control (PPL: PE9445FC2). Result There is a significant increase in expression of HA-dependent adhesion molecules seen in CD44, RHAMM and ICAM-1 in CRC (p=<0.0001). Whilst Non-HA-dependent adhesion molecules demonstrated either significant downregulation or no expression difference. Cellular adhesion was decreased in three CRC cell lines when treated with HAi or excess HA. Treatment with HAi and HA in-vivo confirmed a significant reduction in PM, compared to controls (HAi p=0.0094, HA p=0.0009). Conclusion HA-dependent adhesion molecules and HA appear to play a role in CRC. Targeting HA-dependent interaction in CRC influences cellular adhesion and may have a potential therapeutic use in treatment of PM in CRC. Further in-vitro and in vivo modelling is needed. Take-home message HA receptor adhesion molecules CD44, RHAMM and ICAM-1 have all been independently implicated in adverse outcomes in colorectal cancer. Targeting HA receptor interaction appears to reduce peritoneal dissemination in colorectal cancer.

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HYALURONIC ACID PATHWAY EXPRESSION IN PAIRED EUTOPIC ENDOMETRIAL AND ENDOMETRIOMA CELLS

Fertility and Sterility ◽

10.1016/j.fertnstert.2021.07.555 ◽

2021 ◽

Vol 116 (3) ◽

pp. e202-e203

Author(s):

Kathryn M. Goldrick ◽

Jennifer F. Knudtson ◽

Mubeen Sultana ◽

Rajeshwar Rao Tekmal ◽

Robert S. Schenken

Keyword(s):

Hyaluronic Acid ◽

Pathway Expression ◽

Acid Pathway

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Segregation of cell adhesion molecules into membrane microdomains facilitates leukocyte-endothelial interactions

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100140270 ◽

1995 ◽

Vol 53 ◽

pp. 780-781

Author(s):

S.L. Erlandsen

Keyword(s):

Cell Surface ◽

Adhesion Molecules ◽

Colloidal Gold ◽

High Spatial Resolution ◽

Low Voltage ◽

Cellular Adhesion ◽

Membrane Microdomains ◽

Immunogold Label ◽

Cellular Adhesion Molecules ◽

Electron Detection

Cells interact with their extracellular environments by means of a variety of cellular adhesion molecules (CAM) and surface ligands. In many instances, CAMs interact in a sequential temporal fashion which suggests that these adhesion molecules may occupy or be polarized to various membrane microdomains on the cell surface. Detection of CAMs can be accomplished by a variety of methods including immunofluorescent microscopy and flow cytometry, and by the use of immunocytochemical markers (i.e. colloidal gold) in electron microscopy. The development of high resolution field emission SEM in the mid 1980's and the Autrata modification of the YAG detector for backscatter electron detection at low voltage has greatly facilitated the recognition of colloidal gold probes for detection of surface CAMs. Low voltage FESEM with Bse imaging provides increased resolution of cell surface topography (~3nm at 3-4 keV) which can be observed in 3-dimensions, and simultaneously permits detection/high spatial resolution of immunogold label by atomic number contrast.

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