Review
doi: 10.1007/s00018-011-0782-7. Epub 2011 Aug 20.Roles for CCN2 in normal physiological processes
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- PMID:21858450
- PMCID: PMC3670951
- DOI: 10.1007/s00018-011-0782-7
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Review
Roles for CCN2 in normal physiological processes
Faith Hall-Glenn et al. Cell Mol Life Sci.2011 Oct.
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Abstract
CCN2, also known as connective tissue growth factor, is a member of the CCN (CCN1-6) family of modular matricellular proteins. Analysis of CCN2 function in vivo has focused primarily on its key role as a mediator of excess ECM synthesis in multiple fibrotic diseases. However, CCN2 and related family members are widely expressed during development. Recent studies using new genetic models are revealing that CCN2 has essential roles in the development of many tissues. This review focuses on current and emerging data on CCN2 and its functions in chondrogenesis and angiogenesis, and on new studies showing that CCN2 has essential functions during embryonic and postnatal development in a number of epithelial tissues.
© Springer Basel AG 2011
Figures
Functional Domains of CCN Family Members. The CCN family is comprised of six members that contain four conserved functional domains. Each domain is likely to contribute both independently and cooperatively to the overall function of the CCN family members. The insulin-like growth factor binding protein (IGFBP) domain and the von Willebrand factor C (VWC) domain both bind to aggrecan. The VWC domain also binds to BMPs and TGFβ, integrins and matrix metalloproteinases (MMPs). The third motif is the thrombospondin (TSP) domain, which interacts with integrins, growth factors, vascular endothelial growth factor (VEGF) and low-density lipoprotein receptor-related proteins (LRPs). The last structural module is the C-terminal domain, which contains the cysteine knot motif. This motif binds to integrins, heparin sulfate proteoglycans (HSPGs), fibronectin and LRPs. CCN5 lacks this structural motif, but can still function similarly to other CCN family members. Downstream signaling via integrins activates multiple cell signaling pathways that mediate cell survival, migration, and ECM production
CCN2 eGFP Expression in the adult mouse. CCN2 expression was examined in 1-month-old male mice.a Strong CCN2 expression was observed in vertebral bodies and intervertebral discs.b CCN2 is expressed in ribs within the cartilaginous ventral segments, as compared to undetectable expression in the ossified dorsal rib segments.c,c′ Expression in hypertrophic chondrocytes in the femoral growth plate and in articular cartilage.c′ is a magnification of the growth plate inc.d CCN2 is highly expressed in cranial sutures. Expression was also observed in both major and minor vasculature including coronary arteries (e), kidneys (f) and lungs (g). Intervertebral disc (IVD), sternebra (St), rib ventral segment (Rv), rib dorsal segments (Rd), femoral condyle (Fc), vessel (v), hypertrophic chondrocytes (Hc), cranial sutures (Cs), atria (At), coronary artery (Ca), ventricle (Vt), renal cortex (Rc), renal medulla (Rm), bronchus (Br). Images were taken on a Leica MZ 16F bright field/GFP dissecting scope
References
- Vorwerk P, Oh Y, Rosenfeld RG, Shymko RM. Binding properties of insulin-like growth factor binding protein-3 (IGFBP-3), IGFBP-3 N- and C-terminal fragments, and structurally related proteins mac25 and connective tissue growth factor measured using a biosensor. Endocrinology. 2002;143:1677–1685. doi: 10.1210/en.143.5.1677. - DOI - PubMed
- Leu SJ, Lau LF. Proangiogenic activities of CYR61 (CCN1) mediated through integrins avb3 and a6b1 in human umbilical vein endothelial cells. J Biol Chem. 2002;286:25505–25518. - PubMed
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