The extracellular matrix (ECM) consists of a complex glycoprotein assortment and proteoglycan networks that are produced locally by cells in the matrix and are assembled into an organized meshwork, composing the interstitial matrix and the basement membrane. The ECM serves not only as a structural support scaffold for tissues but also regulates cell behavior. Interactions between cells and ECM components influence cell migration, adhesion, differentiation, and proliferation. Inflammatory cell recruitment is mediated by interactions between integrins and several ECM proteins, including fibronectin, vitronectin, and laminin, which function as integrin ligands. Mindin is an F-spondin (FS) family member, multidomain ECM protein, with numerous functions. The FS domain resides at the N-terminus, while the C-terminus features a thrombospondin type 1 repeat. Li and colleagues [1] demonstrated that the FS domain mediates integrin binding and identified the binding site by mutagenesis. Li et al. further showed that mindin recognizes lipopolysaccharide through the thrombospondin repeat domain, and presented evidence that C-mannosylation of this domain influences lipopolysaccharide binding [1]. These complex interactions raised the possibility that mindin could promote activation of both adaptive and innate immune responses. Tan and Lawler [2] investigated the crystal structure of the FS domain and found that the FS domain may be responsible for membrane targeting that could explain mindin's regulation of axonal development. Indeed, mindin and other FS members were shown to promote the outgrowth and adhesion of embryonic hippocampal neurons [3].Mice lacking mindin have an impaired ability to clear bacterial infections, and mindin-deficient macrophages show defective responses to microbial stimuli [4,5]. Mindin binds directly to bacteria and their components and functions as an opsonin for macrophage phagocytosis. Thus, mindin represents a unique pattern recognition molecule in the ECM, as shown in Fig. 1A. Mindin-deficient mice also displayed severely impaired recruitment of neutrophils and macrophages to inflammation sites. Mindin-integrin interactions were also found to have a key function in T cell priming by dendritic cells. The mindin-deficient mice had defective humoral immune responses to T celldependent antigens. The dendritic cells from mindindeficient mice exhibited an impaired capacity to prime CD4+ T cells due to inefficient engagement of T lymphocytes. With this broad role in innate and acquired immunity, it comes as no surprise that mindin has turned in numerous disease processes. For instance, mindin was found in podocytes in a rodent model of diabetic nephropathy [6]. Mindin was also found to modify airway responses in response to noxious agents [7], and now, mindin turns up as an important ECM protein in the heart.In this issue, Bian and colleagues [8] report on the role of mindin in cardiac hypertrophy. They relied on the mindin gene-deleted mouse model. The authors induced cardiac hypertrophy by thoracic ...
