While fibrosis can represent a normal physiologic process, aberrant fibrosis is a pathology that occurs in a number of different disease states. If left unchecked, this abnormal scarring can have devastating consequences, including compromised organ function leading to organ failure. Consequently, fibrosis is a major source of morbidity and mortality across the globe. The pathobiology of fibrosis can vary across disease states, but commonalities in fibrotic responses do exist and represent attractive points for therapeutic intervention.
In groundbreaking work published in Nature Medicine, Indalo’s co-founders elucidated the central importance of specific RGD-binding integrins in the aberrant activation of TGF-β. TGF-β is a cytokine that serves as a master regulator of fibrosis and has been implicated in a variety of fibrotic disease states.
Expression of many RGD-binding integrins is elevated in fibrotic lesions, with a unique constellation displayed on different cell types. The pro-fibrotic role played by multiple RGD-binding integrins is supported by the profound anti-fibrotic effects achieved through their genetic depletion and pharmacologic modulation in preclinical models. Collectively, these results suggest that specifically targeting appropriate subsets of RGD-binding integrins may represent an attractive therapeutic strategy.