Accumulation of versican facilitates wound healing: Implication of its initial ADAMTS-cleavage site

Islam, Shamima; Chuensirikulchai, Kantinan; Khummuang, Saichit; Keratibumrungpong, Tanyaporn; Kongtawelert, Prachya; Kasinrerk, Watchara; Hatano, Sonoko; Nagamachi, Akiko; Honda, Hiroaki; Watanabe, Hideto

doi:10.1016/j.matbio.2019.10.006

Cited by 48 publications

(40 citation statements)

References 41 publications

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“…Versican is essential during development (76,77) and it is now becoming apparent that it is an important component of the tissue inflammation caused by infection and tissue injury (10). Versican accumulates as part of the early inflammatory response in a number of human diseases often associated with the invasion of leukocytes including those in the vascular system (10,40,(78)(79)(80)(81)(82)(83)(84), lung (5,6,60,77,(85)(86)(87)(88)(89), brain and spinal cord (53,(90)(91)(92), intestine (93)(94)(95)(96), heart (97), liver (63), skin (98,99), eye (100, 101), pancreatic islets (102), and many different forms of cancer [reviewed in (103)(104)(105)]. The accumulation of versican in these tissues is usually associated with other ECM components that bind versican, such as hyaluronan (106,107), link protein, TSG-6, IαI, and CD44 (95, 96, 108-111) (Figure 1).…”

Section: Versican: a Component Of The Inflammatory Responsementioning

confidence: 99%

“…For example, we showed that the G1 fragment of versican promoted extensive ECM cable formation that interconnected adjacent cells and inhibited proliferation, while the intact form had no activity (150). Using the CRISPR/Cas9 system, Hideto Watanabe's group recently developed mice that synthesized versican lacking the ADAMTS versicanase cleavage site (99). They found that accumulation of intact versican in these mice facilitated TGFβ activity coupled to fibroblast proliferation and myofibroblast differentiation and accelerated wound healing.…”

Section: Versican: Interplay With Leukocytesmentioning

confidence: 99%

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Versican—A Critical Extracellular Matrix Regulator of Immunity and Inflammation

et al. 2020

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Section: Versican: a Component Of The Inflammatory Responsementioning

confidence: 99%

Section: Versican: Interplay With Leukocytesmentioning

confidence: 99%

Versican—A Critical Extracellular Matrix Regulator of Immunity and Inflammation

et al. 2020

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“…Based on our studies, we have proposed a uniform autoantigenicity mechanism by which autoAgs share a common biochemical property in their affinity to dermatan sulfate (DS), and by which autoAgs forming a molecular complex with DS to induce autoreactive B cell responses [ 1 – 5 ]. DS, a glycosaminoglycan polysaccharide, is expressed most abundantly in the skin and other connective tissues [ 6 ], and its expression has been reported to increase during high cellular turnaround, such as wound healing [ 7 – 9 ]. It is possible that DS is upregulated to facilitate dead cell clearance and new cell growth for tissue regeneration.…”

Section: Introductionmentioning

confidence: 99%

A proteomic repertoire of autoantigens identified from the classic autoantibody clinical test substrate HEp-2 cells

Wang¹,

Zhang

Rho³

et al. 2020

Clin Proteom

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Background Autoantibodies are a hallmark of autoimmune diseases. Autoantibody screening by indirect immunofluorescence staining of HEp-2 cells with patient sera is a current standard in clinical practice. Differential diagnosis of autoimmune disorders is based on commonly recognizable nuclear and cytoplasmic staining patterns. In this study, we attempted to identify as many autoantigens as possible from HEp-2 cells using a unique proteomic DS-affinity enrichment strategy. Methods HEp-2 cells were cultured and lysed. Total proteins were extracted from cell lysate and fractionated with DS-Sepharose resins. Proteins were eluted with salt gradients, and fractions with low to high affinity were collected and sequenced by mass spectrometry. Literature text mining was conducted to verify the autoantigenicity of each protein. Protein interaction network and pathway analyses were performed on all identified proteins. Results This study identified 107 proteins from fractions with low to high DS-affinity. Of these, 78 are verified autoantigens with previous reports as targets of autoantibodies, whereas 29 might be potential autoantigens yet to be verified. Among the 107 proteins, 82 can be located to nucleus and 15 to the mitotic cell cycle, which may correspond to the dominance of nuclear and mitotic staining patterns in HEp-2 test. There are 55 vesicle-associated proteins and 12 ribonucleoprotein granule proteins, which may contribute to the diverse speckled patterns in HEp-2 stains. There are also 32 proteins related to the cytoskeleton. Protein network analysis indicates that these proteins have significantly more interactions among themselves than would be expected of a random set, with the top 3 networks being mRNA metabolic process regulation, apoptosis, and DNA conformation change. Conclusions This study provides a proteomic repertoire of confirmed and potential autoantigens for future studies, and the findings are consistent with a mechanism for autoantigenicity: how self-molecules may form molecular complexes with DS to elicit autoimmunity. Our data contribute to the molecular etiology of autoimmunity and may deepen our understanding of autoimmune diseases.

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“…Another study reported that an overabundance of cell-derived versican in the ECM, due to lack of metalloprotease cleavage, promoted myofibroblast formation in mouse dermal fibroblasts. 52 The hyaladherin TNFα-stimulated gene-6 (TSG-6) was shown to crosslink hyaluronan and rigidify hyaluronan films. 53 Interestingly, CD44, the receptor for hyaluronan, is more fluid in the membrane of fibroblasts versus myofibroblasts 54 raising the question of whether increased cell-associated HAPLN1 following TGF-β1 induction stabilizes the ECM and could affect CD44 fluidity and cortical actin from outside the cell.…”

Section: Discussionmentioning

confidence: 99%

A Role for HAPLN1 During Phenotypic Modulation of Human Lung Fibroblasts In Vitro

Evanko

Gooden

Kang

et al. 2020

J Histochem Cytochem.

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Hyaluronan and proteoglycan link protein 1 (HAPLN1) stabilizes interactions between two important extracellular matrix (ECM) macromolecules, versican and hyaluronan, which facilitate proliferation of fibroblasts and their conversion to myofibroblasts. However, the role of HAPLN1 in these events has not been studied. Using immunocytochemistry, cellular and ECM locations of HAPLN1 were evaluated in cultured human lung fibroblasts during proliferation and conversion to myofibroblasts. HAPLN1 localized to pericellular matrices, associating with both versican and hyaluronan in the ECM and on the cell surface. Nuclear and total HAPLN1 immunostaining increased after myofibroblast induction. Confocal microscopy showed HAPLN1 predominant in the ECM under cells while versican predominated above cells. Versican and HAPLN1 were also juxtaposed in columnar inclusions in the cytoplasm and nucleus. Nuclear HAPLN1 staining in interphase cells redistributed to the cytosol during mitosis. In the absence of TGF-β1, addition of exogenous bovine HAPLN1 (together with aggrecan G1) facilitated myofibroblast formation, as seen by significant upregulation of α-smooth muscle actin (SMA) staining, while adding full-length bovine versican had no effect. Increased compaction of hyaluronan-rich ECM suggests that HAPLN1 plus G1 addition affects hyaluronan networks and myofibroblast formation. These observations demonstrate changes in both extracellular and intracellular localization of HAPLN1 during fibroblast proliferation and myofibroblast conversion suggesting a possible role in fibrotic remodeling:

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Accumulation of versican facilitates wound healing: Implication of its initial ADAMTS-cleavage site

Cited by 48 publications

References 41 publications

Versican—A Critical Extracellular Matrix Regulator of Immunity and Inflammation

Versican—A Critical Extracellular Matrix Regulator of Immunity and Inflammation

A proteomic repertoire of autoantigens identified from the classic autoantibody clinical test substrate HEp-2 cells

A Role for HAPLN1 During Phenotypic Modulation of Human Lung Fibroblasts In Vitro

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