Cysteine-rich Protein 61 (CCN1) Domain-specific Stimulation of Matrix Metalloproteinase-1 Expression through αVβ3 Integrin in Human Skin Fibroblasts

Qin, Zhaoping; Fisher, Gary J.; Quan, Taihao

doi:10.1074/jbc.m112.424358

Cited by 34 publications

(32 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In cultured human dermal fibroblasts, the elevated expression of CCN1 not only inhibits the expression of type I procollagen, but also concurrently increases the expression of multiple MMPs and cytokines [36,38,39,77].…”

Section: Ccn1 Functions As a Critical Mediator Of Oxidative Stress-inmentioning

confidence: 99%

“…As described below, oxidative stress can result in the following: inducing multiple matrix metalloproteinases (MMPs), which cause fragmentation of collagen fibrils [7,20,[36][37][38][39][40]; inhibiting TGF-β signaling, which causes inhibition of the collagenous ECM production [1,39,41]; and inducing multiple age-related pro-inflammatory cytokines, which create an inflammatory dermal microenvironment (inflammaging) [35,39,42]. These ROS-induced alterations of the dermal ECM microenvironment are the driving force for the most prominent clinical features of aged skin, including thinning and increased fragility of the skin [5,7,8,20,[43][44][45].…”

Section: Collagen Fragmentation Collapses Dermal Fibroblasts and Incrmentioning

confidence: 99%

See 1 more Smart Citation

Oxidative Stress and Human Skin Connective Tissue Aging

Quan

2016

Cosmetics

Self Cite

View full text Add to dashboard Cite

Everyone desires healthy and beautiful-looking skin. However, as we age, our skin becomes old due to physiological changes. Reactive oxygen species (ROS) is an important pathogenic factor involved in human aging. Human skin is exposed to ROS generated from both extrinsic sources such as as ultraviolet (UV) light from the sun, and intrinsic sources such as endogenous oxidative metabolism. ROS-mediated oxidative stress damages the collagen-rich extracellular matrix (ECM), the hallmark of skin connective tissue aging. Damage to dermal collagenous ECM weakens the skin's structural integrity and creates an aberrant tissue microenvironment that promotes age-related skin disorders, such as impaired wound healing and skin cancer development. Here, we review recent advances in our understanding of ROS/oxidative stress and skin connective tissue aging.

show abstract

Section: Ccn1 Functions As a Critical Mediator Of Oxidative Stress-inmentioning

confidence: 99%

Section: Collagen Fragmentation Collapses Dermal Fibroblasts and Incrmentioning

confidence: 99%

Oxidative Stress and Human Skin Connective Tissue Aging

Quan

2016

Cosmetics

Self Cite

View full text Add to dashboard Cite

show abstract

“…1F). CCN1 protein is composed of five distinct domains, and the domain-specific function plays essential roles in the pathogenesis of multiple human diseases (15,39). To determine whether a specific domain of CCN1 protein mediated its exosome-shuttled secretion after CSE, five CCN1 constructs were generated in which one of the specific domains was deleted (Fig.…”

Section: Cs Augmented Ccn1 Secretion and Induced Ccn1 Cleavage In Lunmentioning

confidence: 99%

CCN1 secretion and cleavage regulate the lung epithelial cell functions after cigarette smoke

Moon

Kim

Gao

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

View full text Add to dashboard Cite

show abstract

“…In this study, we mapped the CCN1 epitope for 093G9, which is located in the IGFBP domain of CCN1. Consistently, it has been shown that the IGFBP domain of CCN1 is required for CCN1 to stimulate MMP1 expression . However, little is known about the molecular mechanisms underlying the multifaceted CCN1 functions yet.…”

Section: Discussionmentioning

confidence: 84%

Molecular basis for the recognition of CCN1 by monoclonal antibody 093G9

Zhong

Huo

et al. 2017

J of Molecular Recognition

View full text Add to dashboard Cite

CCN1, also named Cyr61 (cysteine-rich protein 61), is the first identified member of the CCN family that is composed of 6 secreted extracellular matrix-associated glycoproteins. CCN1 has been demonstrated to participate in pathogenesis of rheumatoid arthritis through various pathways. A monoclonal antibody, namely, 093G9, is effective to antagonize the effects of CCN1 and hence has potential therapeutic benefits against rheumatoid arthritis. Here, we show that the epitope recognized by 093G9 is mapped to residues 77 to 80 of CCN1, and a cyclic peptide encompassing residues 75 to 81 of CCN1 displays high binding affinity for 093G9. The crystal structure of the 093G9 Fab in complex with the cyclic peptide was determined at 2.7 Å resolution, which reveals the intensive interactions between CCN1 and 093G9. Particularly, residues Asn79 and Phe80 of CCN1 are inserted into cavities mainly formed by residues of complementarity-determining region loop L3 and framework region L2 and by residues of complementarity-determining region loops H2 and H3, respectively, which contribute most of the interactions and therefore are critical for the recognition by 093G9. Together, these findings not only identify the epitope of CCN1 for 093G9 but also reveal the molecular mechanism of recognition and binding of CCN1 by 093G9.

show abstract

Cysteine-rich Protein 61 (CCN1) Domain-specific Stimulation of Matrix Metalloproteinase-1 Expression through αVβ3 Integrin in Human Skin Fibroblasts

Cited by 34 publications

References 42 publications

Oxidative Stress and Human Skin Connective Tissue Aging

Oxidative Stress and Human Skin Connective Tissue Aging

CCN1 secretion and cleavage regulate the lung epithelial cell functions after cigarette smoke

Molecular basis for the recognition of CCN1 by monoclonal antibody 093G9

Contact Info

Product

Resources

About