Of TGF-b1 in regulating expression of MMP-9 in brain astrocytes, which
Of TGF-b1 in regulating expression of MMP-9 in brain astrocytes, which is involved in physiological and pathological tissue remodeling of central nervous system.Background Matrix metalloproteinases (MMPs) are a large family of zinc-dependent endopeptidases that play an important role in the turnover of extracellular matrix (ECM) and function in physiological and pathological processes [1]. In the central nervous system (CNS), MMPs, and MMP-9 especially, are implicated in Sitravatinib supplier development, morphogenesis, wounding healing, neurite outgrowth, and immune cell migration [2]. In addition, they also participate in the pathogenesis of several CNS diseases such as* Correspondence: [email protected] 2 Department of Pharmacology, Chang Gung University, Tao-Yuan, Taiwan Full list of author information is available at the end of the articlestroke, Alzheimer’s disease, neuroinflammation, and malignant glioma [3]. Among members of the MMP family, MMP-9 has been shown to be elevated in various brain disorders [4-6]. Moreover, several pro-inflammatory mediators such as interleukin-1b (IL-1b), lipopolysaccharide, bradykinin (BK), and oxidized lowdensity lipoprotein (oxLDL) can induce MMP-9 expression and activity in cultured rat astrocytes [7-10], indicating that the expression and activation of MMP-9 may be regulated during brain injuries and inflammation. Transforming growth factor-b (TGF-b) is a multifunctional cytokine that regulates a broad diversity of physiological and pathological processes, including tissue?2010 Hsieh et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Hsieh et al. Journal of Neuroinflammation 2010, 7:88 http://www.jneuroinflammation.com/content/7/1/Page 2 ofwound healing, inflammation, cell proliferation, differentiation, migration, and extracellualr matrix (ECM) synthesis [11-13]. Accordingly, TGF-b family members play an important role in early embryogenesis and in the homeostasis of adult tissues. However, several lines of evidence show that lack of coordination of TGF-bdependent signaling often leads to a number of human diseases, including fibrosis [14,15], cancer [16,17], and autoimmune diseases [18]. Moreover, TGF-b is a key immune system modulator, TGF-b1 especially, that may have both pro- and anti-inflammatory effects in immune system depending on the cell type (11-13). Within the PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26437915 CNS, all three isoforms of TGF-bs family, i.e. TGF-b1, -b2, and -b3, are produced by both glial and neural cells [19]. Previous reports have suggested a relationship between increased TGF-b1 levels and cerebral ischemic PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26162776 injury [20,21]. Following CNS injury, elevated TGF-b levels in astrocytes has been proven to be associated with astrocytic scar formation [22]. Emerging evidence has also demonstrated that TGF-b1 is a crucial mediator in the pathogenesis of several CNS disorders, such as in organization of glial scars in response to injury and in several neurodegenerative disorders [11,15,23]. TGF-bs binds to two serine/threonine kinase receptors which consist of TGF-bRI and TGF-bRII. When a ligand binds, TGF-bRII phosphorylates TGF-bRI and activates Smad-dependent intracellular signaling pathways and thus leads to expression of several genes [24-26]. In addition to activation of Smad-dep.
