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Augmentation of integrin-mediated mechanotransduction by hyaluronic acid.

ABSTRACT: Changes in tissue and organ stiffness occur during development and are frequently symptoms of disease. Many cell types respond to the stiffness of substrates and neighboring cells in vitro and most cell types increase adherent area on stiffer substrates that are coated with ligands for integrins or cadherins. In vivo cells engage their extracellular matrix (ECM) by multiple mechanosensitive adhesion complexes and other surface receptors that potentially modify the mechanical signals transduced at the cell/ECM interface. Here we show that hyaluronic acid (also called hyaluronan or HA), a soft polymeric glycosaminoglycan matrix component prominent in embryonic tissue and upregulated during multiple pathologic states, augments or overrides mechanical signaling by some classes of integrins to produce a cellular phenotype otherwise observed only on very rigid substrates. The spread morphology of cells on soft HA-fibronectin coated substrates, characterized by formation of large actin bundles resembling stress fibers and large focal adhesions resembles that of cells on rigid substrates, but is activated by different signals and does not require or cause activation of the transcriptional regulator YAP. The fact that HA production is tightly regulated during development and injury and frequently upregulated in cancers characterized by uncontrolled growth and cell movement suggests that the interaction of signaling between HA receptors and specific integrins might be an important element in mechanical control of development and homeostasis.

SUBMITTER: Chopra A

PROVIDER: S-EPMC3930571 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Augmentation of integrin-mediated mechanotransduction by hyaluronic acid.

Chopra Anant A Murray Maria E ME Byfield Fitzroy J FJ Mendez Melissa G MG Halleluyan Ran R Restle David J DJ Raz-Ben Aroush Dikla D Galie Peter A PA Pogoda Katarzyna K Bucki Robert R Marcinkiewicz Cezary C Prestwich Glenn D GD Zarembinski Thomas I TI Chen Christopher S CS Puré Ellen E Kresh J Yasha JY Janmey Paul A PA

Biomaterials 20131010 1

Changes in tissue and organ stiffness occur during development and are frequently symptoms of disease. Many cell types respond to the stiffness of substrates and neighboring cells in vitro and most cell types increase adherent area on stiffer substrates that are coated with ligands for integrins or cadherins. In vivo cells engage their extracellular matrix (ECM) by multiple mechanosensitive adhesion complexes and other surface receptors that potentially modify the mechanical signals transduced a ...[more]

PMID: 24120037

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Project description:Introduction: The lips and the mouth play an indispensable role in vocalization, mastication and face aesthetics. Various noxious factors may alter and destruct the original structure, and appearance of the lips and the anatomical area surrounding the mouth. The application of hyaluronic acid (HA) may serve as a safe method for lip regeneration. Although a number of studies exist for HA effectiveness and safety, its beneficial effect is not well-established. Aim: The present meta-analysis and systematic review was performed to investigate the effectiveness of HA on lip augmentation. We also investigated the types and nature of adverse effects (AEs) of HA application. Methods: We reported our meta-analysis in accordance with the PRISMA Statement. PROSPERO protocol registration: CRD42018102899. We performed the systematic literature search in CENTRAL, Embase, and MEDLINE. Randomized controlled trials, cohort studies, case series and case reports were included. The untransformed proportion (random-effects, DerSimonian-Laird method) of responder rate to HA injection was calculated. For treatment related AEs descriptive statistics were used. Results: The systematic literature search yielded 32 eligible records for descriptive statistics and 10 records for quantitative synthesis. The results indicated that the overall estimate of responders (percentage of subjects with increased lip fullness by one point or higher) was 91% (ES = 0.91, 95% CI:0.85-0.96) 2 months after injection. The rate of responders was 74% (ES = 0.74, 95% CI:0.66-0.82) and 46% (ES = 0.46, 95% CI:0.28-0.65) after 6 and 12 months, respectively. We included 1,496 participants for estimating the event rates of AEs. The most frequent treatment-related AEs were tenderness (88.8%), injection site swelling (74.3%) and bruising (39.5%). Rare AEs included foreign body granulomas (0.6%), herpes labialis (0.6%) and angioedema (0.3%). Conclusion: Our meta-analysis revealed that lip augmentation with injectable HA is an efficient method for increasing lip fullness for at least up to 6 months after augmentation. Moreover, we found that most AEs of HA treatment were mild or moderate, but a small number of serious adverse effects were also found. In conclusion, further well-designed RCTs are still needed to make the presently available evidence stronger.

Dataset Information

Augmentation of integrin-mediated mechanotransduction by hyaluronic acid.

Publications

Augmentation of integrin-mediated mechanotransduction by hyaluronic acid.

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