CHAPTER 7: Galectin-3 Involvement in Fibrotic Diseases

A variety of signaling pathways contribute to initiating the pathologies associated with fibrotic disease. Galectins are a group of beta-galactoside-binding proteins that are involved in a host of cellular processes, some of which contribute to fibrosis in different organs. Accumulating evidence indicates that of these, Galectin-3 (Gal-3) is a pathogenic mediator in fibrotic diseases in many different organs. The atypical Gal-3 contains a single carbohydrate recognition domain (CRD) attached to an N-terminal peptide sequence that putatively nucleates the formation of oligomers that can form lattice networks when bound to multiple cellular glycans. Pharmacological or genetic knockdown of Gal-3 has been shown to inhibit fibrosis in several organs, and thus has emerged as a valid therapeutic target. This chapter will review the structure and function of Gal-3 and attempt to validate the important role it plays in fibrosis. In addition, the current state of pharmaceutical discovery of Gal-3 inhibitors will be outlined and discussed in the context of fibrotic disease of the heart, liver, lungs and kidneys. A discussion of the challenges facing future Gal-3 inhibitor development for targeting fibrosis will also be included.