The Influence of the Extracellular Matrix in Inflammation: Findings from the SPARC‐Null Mouse

Abstract

Matricellular proteins are secreted proteins that, among other functions, can contribute to extracellular matrix (ECM) assembly including modulation of cell:ECM interactions. Recent discoveries have indicated a fundamental role for the ECM in the regulation of inflammatory responses including cell extravasation and recruitment, immune cell differentiation, polarization, activation, and retention in tissues. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular collagen-binding protein implicated in fibrillar collagen assembly in the ECM of connective tissue as well as in basal lamina organization. Functions of SPARC in modulating cell adhesion events are also reported. Studies of phenotypic responses observed in SPARC-null mice to a variety of injury models have yielded interesting insight into the functional importance of SPARC production and aberrations in ECM structure that occur in the absence of SPARC that influence immune cell behavior and inflammatory pathways. In this review, we will discuss several examples from different tissues in which SPARC-null mice exhibited an inflammatory response distinct from those of SPARC expressing mice and provide insight into novel ECM-dependent mechanisms that influence these responses.

Secreted Protein Acidic and Rich in Cysteine: Metabolic and Homeostatic Properties beyond the Extracellular Matrix Structure

“…All these elements show how targeting the ECM or its associated proteins could impact the energy balance and the metabolic paths. Fortunately, cellular and animal models, including those of the knock-out of Sparc, shed light on the roles the ECM and its associated proteins (such as collagen) have within different contexts [45][46][47][48]. Secreted protein acidic and rich in cysteine (SPARC) metabolic and homeostatic implications.…”

“…This would result in a cellular profile adapted to the changes that tissues undergo in terms of energy usage and storage and homeostatic needs. Moreover, the implications of the ECM [46] or SPARC [49][50][51][52] in other nonstructural functions such as inflammation, immunity, and cell growth would not only emphasize the importance of uncovering more pathways that ECM and SPARC govern but would also strengthen knowledge of metabolics, especially of links that have been established between cytokine (involved in inflammation and immunity) and metabolism [53][54][55]. Herein, cancer would be an illustrative example of such a "cell development-metabolism synchronization".…”

SPARC in Breast Carcinomas: A Critical Review

“…Riley and Bradshaw 18 in a recent study have discussed diverse mechanisms through which SPARC modulates the assembly and arrangement of collagens and basal lamina; their alteration is noticed in SPARC-null mice. An effective arrangement of fibronectin (Fn) matrix is mandatory for ECM maturation.…”

Extracellular matrix: The proteins that function throughout the body

“…The role of ECM in inflammation is addressed in the article describing the phenotype of the secreted protein acidic and rich in cysteine (SPARC)‐null mouse. SPARC is a matricellular collagen‐binding protein associated with fibrillar collagen and basal lamina assembly (Riley and Bradshaw, 2020). The SPARC null mice have an altered immune response and aberrations in the ECM structure.…”