Hyaluronic acid induces transglutaminase II to enhance cell motility; role of Rac1 and FAK in the induction of transglutaminase II

AbstractIn inflamed joints, enhanced hyaluronic acid (HA) degradation is closely related to the pathogenesis of rheumatoid arthritis (RA). KIAA1199 has been identified as a hyaladherin that mediates the intracellular degradation of HA, but its extracellular function remains unclear. In this study, we found that the serum and synovial levels of secreted KIAA1199 (sKIAA1199) and low-molecular-weight HA (LMW-HA, MW < 100 kDa) in RA patients were significantly increased, and the positive correlation between them was shown for the first time. Of note, treatment with anti-KIAA1199 mAb effectively alleviated the severity of arthritis and reduced serum LMW-HA levels and cytokine secretion in collagen-induced arthritis (CIA) mice. In vitro, sKIAA1199 was shown to mediate exogenous HA degradation by attaching to the cell membrane of RA fibroblast-like synoviosytes (RA FLS). Furthermore, the HA-degrading activity of sKIAA1199 depended largely on its adhesion to the membrane, which was achieved by its G8 domain binding to ANXA1. In vivo, kiaa1199-KO mice exhibited greater resistance to collagen-induced arthritis. Interestingly, this resistance could be partially reversed by intra-articular injection of vectors encoding full-length KIAA1199 instead of G8-deleted KIAA119 mutant, which further confirmed the indispensable role of G8 domain in KIAA1199 involvement in RA pathological processes. Mechanically, the activation of NF-κB by interleukin-6 (IL-6) through PI3K/Akt signaling is suggested to be the main pathway to induce KIAA1199 expression in RA FLS. In conclusion, our study supported the contribution of sKIAA1199 to RA pathogenesis, providing a new therapeutic target for RA by blocking sKIAA1199-mediated HA degradation.

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Role of the Fill and Lift Effect with Hyaluronic ACID on the Middle Third of the Face: What Are the Effects on the Lower Eyelid?

Aesthetic Plastic Surgery ◽

10.1007/s00266-021-02340-1 ◽

2021 ◽

Author(s):

Mauro Barone ◽

Rosa Salzillo ◽

Paolo Persichetti

Keyword(s):

Hyaluronic Acid ◽

Lower Eyelid ◽

The Face

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Role of the V1G1 subunit of V-ATPase in breast cancer cell migration

Scientific Reports ◽

10.1038/s41598-021-84222-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Maria De Luca ◽

Roberta Romano ◽

Cecilia Bucci

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Cell Motility ◽

Cancer Progression ◽

Tumor Formation ◽

Downstream Signaling ◽

Late Endosomes ◽

Intracellular Compartments

AbstractV-ATPase is a large multi-subunit complex that regulates acidity of intracellular compartments and of extracellular environment. V-ATPase consists of several subunits that drive specific regulatory mechanisms. The V1G1 subunit, a component of the peripheral stalk of the pump, controls localization and activation of the pump on late endosomes and lysosomes by interacting with RILP and RAB7. Deregulation of some subunits of the pump has been related to tumor invasion and metastasis formation in breast cancer. We observed a decrease of V1G1 and RAB7 in highly invasive breast cancer cells, suggesting a key role of these proteins in controlling cancer progression. Moreover, in MDA-MB-231 cells, modulation of V1G1 affected cell migration and matrix metalloproteinase activation in vitro, processes important for tumor formation and dissemination. In these cells, characterized by high expression of EGFR, we demonstrated that V1G1 modulates EGFR stability and the EGFR downstream signaling pathways that control several factors required for cell motility, among which RAC1 and cofilin. In addition, we showed a key role of V1G1 in the biogenesis of endosomes and lysosomes. Altogether, our data describe a new molecular mechanism, controlled by V1G1, required for cell motility and that promotes breast cancer tumorigenesis.

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The Role of Hyaluronic Acid in Cartilage Boundary Lubrication

Cells ◽

10.3390/cells9071606 ◽

2020 ◽

Vol 9 (7) ◽

pp. 1606 ◽

Cited By ~ 3

Author(s):

Weifeng Lin ◽

Zhang Liu ◽

Nir Kampf ◽

Jacob Klein

Keyword(s):

Hyaluronic Acid ◽

Synovial Fluid ◽

Surface Force ◽

Force Balance ◽

New Paradigm ◽

Low Friction ◽

Cartilage Surface ◽

Boundary Lubricant ◽

Lipid Layers

Hydration lubrication has emerged as a new paradigm for lubrication in aqueous and biological media, accounting especially for the extremely low friction (friction coefficients down to 0.001) of articular cartilage lubrication in joints. Among the ensemble of molecules acting in the joint, phosphatidylcholine (PC) lipids have been proposed as the key molecules forming, in a complex with other molecules including hyaluronic acid (HA), a robust layer on the outer surface of the cartilage. HA, ubiquitous in synovial joints, is not in itself a good boundary lubricant, but binds the PC lipids at the cartilage surface; these, in turn, massively reduce the friction via hydration lubrication at their exposed, highly hydrated phosphocholine headgroups. An important unresolved issue in this scenario is why the free HA molecules in the synovial fluid do not suppress the lubricity by adsorbing simultaneously to the opposing lipid layers, i.e., forming an adhesive, dissipative bridge between them, as they slide past each other during joint articulation. To address this question, we directly examined the friction between two hydrogenated soy PC (HSPC) lipid layers (in the form of liposomes) immersed in HA solution or two palmitoyl–oleoyl PC (POPC) lipid layers across HA–POPC solution using a surface force balance (SFB). The results show, clearly and surprisingly, that HA addition does not affect the outstanding lubrication provided by the PC lipid layers. A possible mechanism indicated by our data that may account for this is that multiple lipid layers form on each cartilage surface, so that the slip plane may move from the midplane between the opposing surfaces, which is bridged by the HA, to an HA-free interface within a multilayer, where hydration lubrication is freely active. Another possibility suggested by our model experiments is that lipids in synovial fluid may complex with HA, thereby inhibiting the HA molecules from adhering to the lipids on the cartilage surfaces.

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The activity status of cofilin is directly related to invasion, intravasation, and metastasis of mammary tumors

The Journal of Cell Biology ◽

10.1083/jcb.200510115 ◽

2006 ◽

Vol 173 (3) ◽

pp. 395-404 ◽

Cited By ~ 178

Author(s):

Weigang Wang ◽

Ghassan Mouneimne ◽

Mazen Sidani ◽

Jeffrey Wyckoff ◽

Xiaoming Chen ◽

...

Keyword(s):

Cell Motility ◽

Cell Invasion ◽

Actin Polymerization ◽

Cancer Cell Invasion ◽

Invasion And Metastasis ◽

Over Expression ◽

Cell Biol ◽

Tumor Cell Motility ◽

New Strategies

Understanding the mechanisms controlling cancer cell invasion and metastasis constitutes a fundamental step in setting new strategies for diagnosis, prognosis, and therapy of metastatic cancers. LIM kinase1 (LIMK1) is a member of a novel class of serine–threonine protein kinases. Cofilin, a LIMK1 substrate, is essential for the regulation of actin polymerization and depolymerization during cell migration. Previous studies have made opposite conclusions as to the role of LIMK1 in tumor cell motility and metastasis, claiming either an increase or decrease in cell motility and metastasis as a result of LIMK1 over expression (Zebda, N., O. Bernard, M. Bailly, S. Welti, D.S. Lawrence, and J.S. Condeelis. 2000. J. Cell Biol. 151:1119–1128; Davila, M., A.R. Frost, W.E. Grizzle, and R. Chakrabarti. 2003. J. Biol. Chem. 278:36868–36875; Yoshioka, K., V. Foletta, O. Bernard, and K. Itoh. 2003. Proc. Natl. Acad. Sci. USA. 100:7247–7252; Nishita, M., C. Tomizawa, M. Yamamoto, Y. Horita, K. Ohashi, and K. Mizuno. 2005. J. Cell Biol. 171:349–359). We resolve this paradox by showing that the effects of LIMK1 expression on migration, intravasation, and metastasis of cancer cells can be most simply explained by its regulation of the output of the cofilin pathway. LIMK1-mediated decreases or increases in the activity of the cofilin pathway are shown to cause proportional decreases or increases in motility, intravasation, and metastasis of tumor cells.

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The distribution of myosin II in Dictyostelium discoideum slug cells.

The Journal of Cell Biology ◽

10.1083/jcb.115.5.1267 ◽

1991 ◽

Vol 115 (5) ◽

pp. 1267-1274 ◽

Cited By ~ 12

Author(s):

S Eliott ◽

P H Vardy ◽

K L Williams

Keyword(s):

Cell Motility ◽

Dictyostelium Discoideum ◽

Immunofluorescence Microscopy ◽

Molecular Genetic ◽

Myosin Ii ◽

Three Dimensional ◽

Homogeneous Distribution ◽

Multicellular Development ◽

Insight Into

While the role of myosin II in muscle contraction has been well characterized, less is known about the role of myosin II in non-muscle cells. Recent molecular genetic experiments on Dictyostelium discoideum show that myosin II is necessary for cytokinesis and multicellular development. Here we use immunofluorescence microscopy with monoclonal and polyclonal antimyosin antibodies to visualize myosin II in cells of the multicellular D. discoideum slug. A subpopulation of peripheral and anterior cells label brightly with antimyosin II antibodies, and many of these cells display a polarized intracellular distribution of myosin II. Other cells in the slug label less brightly and their cytoplasm displays a more homogeneous distribution of myosin II. These results provide insight into cell motility within a three-dimensional tissue and they are discussed in relation to the possible roles of myosin II in multicellular development.

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Microtubules rich in modified alpha-tubulin characterize the tail processes of motile fibroblasts

Journal of Cell Science ◽

10.1242/jcs.94.2.227 ◽

1989 ◽

Vol 94 (2) ◽

pp. 227-236

Author(s):

A.R. Prescott ◽

M. Vestberg ◽

R.M. Warn

Keyword(s):

Cell Motility ◽

Immunofluorescence Microscopy ◽

Fibroblast Cell ◽

Microscopy Study ◽

Post Translational Modifications ◽

Alpha Tubulin ◽

Major Species ◽

Cytoplasmic Tails ◽

Nih 3T3

The organisation of microtubules rich in post-translationally modified alpha-tubulin has been investigated in a fibroblast cell line (NIH-3T3-T15) that can be reversibly transformed. An immunofluorescence microscopy study of the static non-transformed cells has revealed a central distribution of wavy microtubules showing post-translational modifications. When transformed there is a marked increase in cell motility and the appearance of long thin cytoplasmic ‘tails’. These tails have been found to contain conspicuous bundles of post-translationally modified microtubules that run down the length of the processes and terminate close to the plasmalemma. Both detyrosinated and acetylated alpha-tubulin are present as major species in these modified microtubules. Such a pattern of modified microtubules is only occasionally seen in the untransformed NIH-3T3-T15 cells. We have also found them to be present in other transformed fibroblast lines. The presence of bundles of microtubules rich in modified alpha-tubulin in the cell tails is correlated with a marked reduction in the numbers of F-actin stress fibres. The possible role of these modified stable microtubules in cell motility is discussed.

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