Decorin Inhibition of PDGF-Stimulated Vascular Smooth Muscle Cell Function

Nili, Nafiseh; Cheema, Asim N.; Giordano, Frank J.; Barolet, Alan; Babaei, Saeid; Hickey, Reed; Eskandarian, Mohammad R.; Smeets, Mirjam B.; Butany, Jagdish; Pasterkamp, Gérard; Strauss, Bradley H.

doi:10.1016/s0002-9440(10)63447-5

Cited by 102 publications

(40 citation statements)

References 38 publications

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“…However, LRP-1 also regulates signaling cascades by binding growth factors such as platelet-derived growth factor (49), CTGF (50), and TGF-␤ (51, 52). Interestingly, several of these molecules also bind decorin (53)(54)(55). Type V TGF-␤ receptor was found to be identical to LRP-1 (56) and mediates its response upon stimulation of insulin-like growth factorbinding protein 3 (IGFBP-3) (56,57).…”

Section: Discussionmentioning

confidence: 99%

A Novel Modulatory Mechanism of Transforming Growth Factor-β Signaling through Decorin and LRP-1

Cabello-Verrugio¹,

Brandan

2007

Journal of Biological Chemistry

114

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Section: Discussionmentioning

confidence: 99%

A Novel Modulatory Mechanism of Transforming Growth Factor-β Signaling through Decorin and LRP-1

Cabello-Verrugio¹,

Brandan

2007

Journal of Biological Chemistry

114

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“…NPN Inhibits TGF-␤/Smad Signaling-It has been reported that several SLRP members, including DCN, interact with a number of growth factors such as TGF-␤ (22, 23), platelet-derived growth factor (30), and insulin-like growth factor-1 (31), and modulate their activities. Because we have identified the NPN gene based on the structural similarity to DCN, we investigated the possible regulatory function of NPN in TGF-␤ signaling.…”

Section: Npn Belongs To a New Class Of The Slrp Family-basedmentioning

confidence: 99%

Nephrocan, a Novel Member of the Small Leucine-rich Repeat Protein Family, Is an Inhibitor of Transforming Growth Factor-β Signaling

Mochida

Parisuthiman

Kaku

et al. 2006

Journal of Biological Chemistry

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In a search of new, small leucine-rich repeat proteoglycan/ protein (SLRP) family members, a novel gene, nephrocan (NPN), has been identified. The gene consists of three exons, and based on the deduced amino acid sequence, NPN has 17 leucine-rich repeat motifs and unique cysteine-rich clusters both in the N and C termini, indicating that this gene belongs to a new class of SLRP family. NPN mRNA was predominantly expressed in kidney in adult mice, and during mouse embryogenesis, the expression was markedly increased in 11-day-old embryos at a time when early kidney development takes place. In the adult mouse kidney, NPN protein was located in distal tubules and collecting ducts. When NPN was overexpressed in cell culture, the protein was detected in the cultured medium, and upon treatment with N-glycosidase F, the molecular mass was lowered by ϳ14 kDa, indicating that NPN is a secreted N-glycosylated protein. Furthermore, transforming growth factor-␤ (TGF-␤)-responsive 3TP promoter luciferase activity was down-regulated, and TGF-␤-induced Smad3 phosphorylation was also inhibited by NPN, suggesting that NPN suppresses TGF-␤/Smad signaling. Taken together, NPN is a novel member of the SLRP family that may play important roles in kidney development and pathophysiology by functioning as an endogenous inhibitor of TGF-␤ signaling.

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“…Importantly, many of these cell functions are controlled by growth factors and cytokines (TGFβ, TNFα and PDGF) that are stored in the ECM and presented to cells as they interact with and remodel the matrix. The types of control mechanisms employed include secretion of growth factors in latent form, storage in the ECM by use of specific binding proteins to prevent receptor binding, activation of latent or bound forms via proteolytic processing [17–19], and modulation of receptor activity [20,21]. Indeed, our previously published studies have shown that ECM proteins regulate MSC behavior by modulating both endogenous (stem cell-derived) and exogenous (externally added or serum-derived) growth factor stores [10,12,14,22].…”

Section: Introductionmentioning

confidence: 99%

One size does not fit all: developing a cell-specific niche for in vitro study of cell behavior

Marinkovic¹,

Block²,

Rakian

et al. 2016

Matrix Biology

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For more than 100 years, cells and tissues have been studied in vitro using glass and plastic surfaces. Over the last 10–20 years, a great body of research has shown that cells are acutely sensitive to their local environment (extracellular matrix, ECM) which contains both chemical and physical cues that influence cell behavior. These observations suggest that modern cell culture systems, using tissue culture polystyrene (TCP) surfaces, may fail to reproduce authentic cell behavior in vitro, resulting in “artificial outcomes.” In the current study, we use bone marrow (BM)- and adipose (AD)-derived stromal cells to prepare BM-ECM and AD-ECM, which are decellularized after synthesis by the cells, to mimic the cellular niche for each of these tissues. Each ECM was characterized for its ability to affect BM- and AD-mesenchymal stem cell (MSC) proliferation, as well as proliferation of three cancer cell lines (HeLa, MCF-7, and MDA-MB-231), modulate cell spreading, and direct differentiation relative to standard TCP surfaces. We found that both ECMs promoted the proliferation of MSCs, but that this effect was enhanced when the tissue-origin of the cells matched that of the ECM (i.e. BM-ECM promoted the proliferation of BM-MSCs over AD-MSCs, and vice versa). Moreover, BM- and AD-ECM were shown to preferentially direct MSC differentiation towards either osteogenic or adipogenic lineage, respectively, suggesting that the effects of the ECM were tissue-specific. Further, each ECM influenced cell morphology (i.e. circularity), irrespective of the origin of the MSCs, lending more support to the idea that effects were tissue specific. Interestingly, unlike MSCs, these ECMs did not promote the proliferation of the cancer cells. In an effort to further understand how these three culture substrates influence cell behavior, we evaluated the chemical (protein composition) and physical properties (architecture and mechanical) of the two ECMs. While many structural proteins (e.g. collagen and fibronectin) were found at equivalent levels in both BM- and AD-ECM, the architecture (i.e. fiber orientation; surface roughness) and physical properties (storage modulus, surface energy) of each were unique. These results, demonstrating differences in cell behavior when cultured on the three different substrates (BM- and AD-ECM and TCP) with differences in chemical and physical properties, provide evidence that the two ECMs may recapitulate specific elements of the native stem cell niche for bone marrow and adipose tissues. More broadly, it could be argued that ECMs, elaborated by cells ex vivo, serve as an ideal starting point for developing tissue-specific culture environments. In contrast to TCP, which relies on the “one size fits all” paradigm, native tissue-specific ECM may be a more rational model to approach engineering 3D tissue-specific culture systems to replicate the in vivo niche. We suggest that this approach will provide more meaningful information for basic research studies of cell behavior as well as cell-based therapeutics.

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Decorin Inhibition of PDGF-Stimulated Vascular Smooth Muscle Cell Function

Cited by 102 publications

References 38 publications

A Novel Modulatory Mechanism of Transforming Growth Factor-β Signaling through Decorin and LRP-1

A Novel Modulatory Mechanism of Transforming Growth Factor-β Signaling through Decorin and LRP-1

Nephrocan, a Novel Member of the Small Leucine-rich Repeat Protein Family, Is an Inhibitor of Transforming Growth Factor-β Signaling

One size does not fit all: developing a cell-specific niche for in vitro study of cell behavior

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