Fig. 5. Mechanism of galectin-3–induced paracrine signaling in epithelial-stromal interactions.

Multiple functions have been ascribed to the basement membrane, a thin and highly cross-linked extracellular matrix that underlies all epithelia. During homeostatic conditions, these include promotion of mechanical strength, and the maintenance of tissue architecture. Disruption of the basement membrane by trauma allows for direct interactions between epithelial cells and stromal fibroblasts, resulting in a cascade of signaling events critical for tissue repair. We propose that galectin-3 of epithelial origin initiates such events by physically interacting with fibroblasts through an as yet unidentified receptor. As a consequence, the stromal fibroblasts begin to synthesize and secrete abundant amounts of IL-1β, which act in a paracrine fashion to regulate the proteolytic microenvironment by activating the MMP9 promoter in epithelial cells. This reciprocal form of communication would be expected to lead to the remodeling of the collagenous extracellular matrix.