Expression of V3 Versican by Rat Arterial Smooth Muscle Cells Promotes Differentiated and Anti-inflammatory Phenotypes

Kang, Inkyung; Barth, Jeremy L.; Sproul, Erin P.; Yoon, Dong Won; Workman, Gail; Braun, Kathleen R.; Argraves, W. Scott; Wight, Thomas N.

doi:10.1074/jbc.m115.657486

Cited by 22 publications

(23 citation statements)

References 69 publications

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“…In addition, we showed that manipulating the expression of versican by overexpressing the V3 isoform in experimentallyinduced atherosclerotic lesions in rabbits significantly reduced macrophage infiltration, inhibiting the development of lipidfilled atherosclerotic lesions (84). Furthermore, our in vitro studies using rat arterial smooth muscle cells demonstrated that the V3 expression effect is anti-inflammatory and decreased the expression of the CS-containing versican isoforms, V0 and V1, and the formation of elastic fibers which are a poor substrate for macrophages (42,43). Such results further support a critical role for versican in myeloid cell accumulation in atherosclerosis and perhaps in other diseases as well (39).…”

Section: Versican: Interplay With Leukocytesmentioning

confidence: 71%

“…Interestingly, the different isoforms exhibit functional differences regarding their impact on cell phenotype, such as the ability of V1 to promote proliferation and inhibit apoptosis, while V2 exhibits antiproliferative activity (37,38). In contrast, V3 regulates ECM assembly and inhibits cell proliferation and migration (39)(40)(41)(42)(43)(44)(45). A new V5 isoform has been recently described and shown to be expressed by injured rat neurons (46).…”

Section: Versicanmentioning

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: Interplay With Leukocytesmentioning

confidence: 71%

Section: Versicanmentioning

confidence: 99%

Versican—A Critical Extracellular Matrix Regulator of Immunity and Inflammation

et al. 2020

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“…34, 35 Versican staining was significantly increased in AscA and AA at both 4 and 14 weeks (4 – 47-fold, P < 0.001). Versican staining was typically highest in regions with PAU and adjacent Mac-2 staining (Figure XIV in the online-only Data Supplement).…”

Section: Resultsmentioning

confidence: 96%

Postnatal Deletion of the Type II Transforming Growth Factor-β Receptor in Smooth Muscle Cells Causes Severe Aortopathy in Mice

Jaffe

et al. 2015

ATVB

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Objective Prenatal deletion of the type II TGF-β receptor (TBRII) prevents normal vascular morphogenesis and smooth muscle cell (SMC) differentiation, causing embryonic death. The role of TBRII in adult SMC is less well studied. Clarification of this role has important clinical implications because TBRII deletion should ablate TGF-β signaling and blockade of TGF-β signaling is envisioned as a treatment for human aortopathies. We hypothesized that postnatal loss of SMC TBRII would cause aortopathy. Approach and Results We generated mice with either of two tamoxifen-inducible SMC-specific Cre (SMC-CreERT2) alleles and homozygous floxed Tgfbr2 alleles. Mice were injected with tamoxifen, and their aortas examined 4 and 14 weeks later. Both SMC-CreERT2 alleles efficiently and specifically rearranged a floxed reporter gene and efficiently rearranged a floxed Tgfbr2 allele, resulting in loss of aortic medial TBRII protein. Loss of SMC TBRII caused severe aortopathy including hemorrhage, ulceration, dissection, dilation, accumulation of macrophage markers, elastolysis, abnormal proteoglycan accumulation, and aberrant SMC gene expression. All areas of the aorta were affected, with the most severe pathology in the ascending aorta. Cre-mediated loss of SMC TBRII in vitro ablated both canonical and noncanonical TGF-β signaling and reproduced some of the gene expression abnormalities detected in vivo. Conclusions SMC TBRII plays a critical role in maintaining postnatal aortic homeostasis. Loss of SMC TBRII disrupts TGF-β signaling, acutely alters SMC gene expression, and rapidly results in severe and durable aortopathy. These results suggest that pharmacologic blockade of TGF-β signaling in humans could cause aortic disease rather than prevent it.

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“…Originally published as Figure 11 Intriguingly, overexpression of the V3 spliced variant of versican lacking GAG-binding regions has been demonstrated to retard inflammatory cytokine production (including CXCL1, CCL20, CCL2) in smooth muscle cells via blockade of epidermal growth factor receptor and NFκB signaling cascades. 140,141 Overexpression of V3 in melanoma cells reduces the rate of tumor growth by decreasing the proliferative index and increasing the apoptotic rate of primary tumor cells. [142][143][144] In addition, expression of a mutant G3ΔEGF construct (the versican G3 domain with deletion of the EGF-like repeats) also results in slower growth, increased apoptotic rate, and lower tumorigenic potential of astrocytoma cells.…”

Section: Versican As a Regulator Of Pulmonary Innate Immunementioning

confidence: 99%

Proteoglycans as Immunomodulators of the Innate Immune Response to Lung Infection

Kang

Chang

Wight

et al. 2018

J Histochem Cytochem.

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Proteoglycans (PGs) are complex, multifaceted molecules that participate in diverse interactions vital for physiological and pathological processes. As structural components, they provide a scaffold for cells and structural organization that helps define tissue architecture. Through interactions with water, PGs enable molecular and cellular movement through tissues. Through selective ionic interactions with growth factors, chemokines, cytokines, and proteases, PGs facilitate the ability of these soluble ligands to regulate intracellular signaling events and to influence the inflammatory response. In addition, recent findings now demonstrate that PGs can activate danger-associated molecular patterns (DAMPs) and other signaling pathways to influence production of many of these soluble ligands, indicating a more direct role for PGs in influencing the immune response and tissue inflammation. This review will focus on PGs that are selectively expressed during lung inflammation and will examine the novel emerging concept of PGs as immunomodulatory regulators of the innate immune responses in lungs.

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Expression of V3 Versican by Rat Arterial Smooth Muscle Cells Promotes Differentiated and Anti-inflammatory Phenotypes

Cited by 22 publications

References 69 publications

Versican—A Critical Extracellular Matrix Regulator of Immunity and Inflammation

Versican—A Critical Extracellular Matrix Regulator of Immunity and Inflammation

Postnatal Deletion of the Type II Transforming Growth Factor-β Receptor in Smooth Muscle Cells Causes Severe Aortopathy in Mice

Proteoglycans as Immunomodulators of the Innate Immune Response to Lung Infection

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