Follistatin-like protein 1 and its role in inflammation and inflammatory diseases
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IMMUNOLOGY AT THE UNIVERSITY OF IOWA
Follistatin-like protein 1 and its role in inflammation and inflammatory diseases Yury Chaly • Bruce Hostager • Sonja Smith Raphael Hirsch
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Raphael Hirsch
Yury Chaly
Ó Springer Science+Business Media New York 2014
Abstract Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein produced mainly by cells of mesenchymal origin. FSTL1 has been shown to play an important role during embryogenesis; FSTL1-deficient mice die at birth from multiple developmental abnormalities. In the last decade, FSTL1 has been identified as a novel inflammatory protein, enhancing synthesis of proinflammatory cytokines and chemokines by immune cells in vitro and in vivo. FSTL1 mediates proinflammatory events in animal models of inflammatory diseases, particularly in collagen-induced arthritis in mice. FSTL1 is elevated in various inflammatory conditions and decreased during the course of treatment. FSTL1 may therefore be a valuable biomarker for such diseases. Moreover, a variety of experiments suggest that targeting of FSTL1 may be useful in the treatment of diseases in which inflammation plays a central role. Keywords
Follistatin-like protein 1 Cytokines Monocytes Macrophages Inflammasome
Introduction Follistatin-like protein 1 (FSTL1), a secreted glycoprotein, also named TSC-36 [transforming growth factor (TGF)b 1stimulated clone 36] or FRP (follistatin-related protein), was originally cloned from the mouse osteoblastic cell line MC3T3-E1 [1]. FSTL1 is widely expressed in human and mouse tissues, although its expression was found to be restricted to cells of non-hematopoietic lineage, in particular to cells of the mesenchymal lineage [2–6]. Recent studies have demonstrated that cells of the mesenchymal lineage may actively regulate immune cell function and exert both pro- and anti-inflammatory effects [7–9]. These effects are mediated by various soluble factors released by cells within the inflammatory milieu. Although the function of FSTL1 is not completely understood, it appears to play roles in the regulation of cell
survival, proliferation, differentiation, migration, organ development, carcinogenesis, and metastasis [10–14]. FSTL1 knockout (KO) mice die at birth and display multiple developmental abnormalities of the respiratory and skeletal system [2, 3, 15]. It has been shown that FSTL1 affects mesenchymal tissue development by regulating signaling induced by proteins of the TGFb superfamily [2, 3, 15]. In the past decade, a number of reports have been published, suggesting a role for FSTL1 in inflammation and the regulation of immune cell function. Specifically, several studies have demonstrated that FSTL1 is important in the pathogenesis of rheumatoid arthritis (RA) and other autoimmune diseases. In this review, we summarize the literature on potential roles of FSTL1 in the inflammatory response.
FSTL1 gene structure Y. Chaly (&) B. Hostager S. Smith R. Hirsch Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, 2191 ML, 500 Newt
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