Biology of Galectin-3

Galectins are a family of soluble β-galactoside-binding lectins that play many important regulatory roles in inflammation, immunologic response, and cancer. Galectin-3 has been the most widely-studied member of the galectin protein family.  One of the more interesting and well characterized effects of galectin-3 is its role in the promotion of fibrosis. Fibrogenesis or scarring is a natural consequence of certain types of injury and inflammation. For example, a fibrous capsule surrounds a bacterial infection in an attempt to contain it. Galectin-3 is responsible for the activation of the fibroblasts—the cells responsible for fibrogenesis. This galectin-3-dependent link between inflammation and fibrosis may have diagnostic and therapeutic implications.

In order to further study the role of galectin-3 in fibroblast activation and fibrosis, a custom pathway network was built using the Ingenuity Pathway Knowledge Base (IPKB; Ingenuity Systems, Redwood City, CA, USA). At the injury site, galectin-3 is secreted into the extracellular space. This, in turn, activates resting fibroblasts into matrix-producing fibroblasts. Fibroblast activation is characterized by the increased expression of certain proteins within and arround the fibroblasts, including the extracellular type 1 collagen α-1 chain.

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Galectin-3 affects the synthesis of new matrix components such as type I collagen and influences the degradation of extracellular matrix components through a set of tissue inhibitor metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs). The pathway network diagram above illustrates the central role that galectin-3 plays in the complex development of fibrosis by regulating the expression of fibrotic matrix components such as α-SMA and COL1A1 and matrix turnover through the regulation of TIMPs and MMPs.

Further Reading

  1. Dumic J, Dabelic S, Flögel M. Galectin-3: an open-ended story. Biochim Biophys Acta. 2006;1760:616-35.
  2. Henderson NC, Sethi T. The regulation of inflammation by galectin-3. Immunol Rev. 2009;230:160-71.
  3. Henderson NC, Mackinnon AC, Farnworth SL, et al. Galectin-3 expression and secretion links macrophages to the promotion of renal fibrosis. Am J Pathol. 2008;172:288-98.
  4. Henderson NC, Mackinnon AC, Farnworth SL, et al. Galectin-3 regulates myofibroblast activation and hepatic fibrosis. Proc Natl Acad Sci. 2006;103:5060-65.
  5. Hsu DK, Dowling CA, Jeng KC, et al. Galectin-3 expression is induced in cirrhotic liver and hepatocellular carcinoma. Int J Cancer. 1999;81:519-26.
  6. Kasper M, Hughes RC. Immunocytochemical evidence for a modulation of galectin-3 (mac2), a carbohydrate binding protein, in pulmonary fibrosis. J Pathol. 1996;179:309-16.
  7. Kim H, Lee J, Hyun JW, et al. Expression and immunohistochemical localization of galectin-3 in various mouse tissues. Cell Biol Int. 2007;31:655-62.
  8. Lambert JM, Lopez EF, Lindsey ML. Macrophage roles following myocardial infarction. Int J Cardiol. 2008;130:147-58.
  9. Nishi Y, Sano H, Kawashima T, et al. Role of galectin-3 in human pulmonary fibrosis. Allergol Int. 2007;56:57-65.
  10. Ochieng J, Furtak V, Lukyanov P. Extracellular functions of galectin-3. Glycoconj J. 2004;19:527-35.
  11. Sano H, Hsu DK, Apgar JR, et al. Critical role of galectin-3 in phagocytosis by macrophages. J Clin Invest. 2003;112:389-97.

For a complete list of related readings, please see our Bibliography.