Expression of integrin and CD44 receptors recognising osteopontin in the normal and LPS‐lesioned rat substantia nigra

Abstract

The multifunctional protein osteopontin (OPN) is expressed in the substantia nigra (SN) and protects nigral dopaminergic neurones against toxic insult in animal models of Parkinson's disease, although the mechanisms involved are uncertain. In the periphery, OPN regulates inflammatory processes by interacting with integrin and CD44 receptors but the presence and distribution of these sites in SN is unknown. We investigated the expression of integrin receptor subunits and CD44 receptors in the normal SN and after induction of inflammation by lipopolysaccharide (LPS), and their interaction with OPN. In normal rat SN, integrin αv , β3 and β1 , and CD44, receptors were expressed on neurones including TH-positive cells but not on glia. LPS administration induced a loss of TH-positive neurones in SN and increased expression of glial cells as shown by GFAP, OX-6 and ED-1 immunoreactivity. In LPS-lesioned SN, there was up-regulation of the expression of integrin β3 and CD44 receptors. Co-localisation studies showed that this related to their increased expression on OX-6-, ED-1- and GFAP-positive cells. Furthermore, OPN interacted with integrin and CD44 receptors in the normal rat SN as demonstrated by co-immunoprecipitation and pull-down techniques. These data show that integrin and CD44 receptors are present on neurones in normal rat SN and that they are up-regulated on glial cells following LPS-mediated inflammation in SN, suggesting that they are functionally important in the inflammatory process. The interaction of OPN with these receptors suggests a role in the neuroprotective effect of this protein in the LPS model of Parkinson's disease.

Extracellular matrix hyaluronan signals via its CD44 receptor in the increased responsiveness to mechanical stimulation

“…It is found in several cell types, throughout the nervous system, such as glial cells (Bignami and Dahl, 1986; Gorlewicz et al, 2009; McKenzie et al, 1982) and neurons (Ailane et al, 2013; Raber et al, 2014), and in the ECM (Dzwonek and Wilczynski, 2015; Finlayson, 2015; Multhaupt et al, 2016; Murai, 2015; Orian-Rousseau and Sleeman, 2014). Moreover, it has been shown to play a role in cell migration and activation during inflammation (Gee et al, 2004), and in neuronal development and plasticity (Kochlamazashvili et al, 2010; Wlodarczyk et al, 2011; Dzwonek and Wilczynski, 2015).…”

Integrin β3 and CD44 levels determine the effects of the OPN-a splicing variant on lung cancer cell growth

“…In addition, ligation of OPN to CD44 increases cell adhesion, invasion, and transformation [13, 31]. OPN directly interacts with integrin β3 and CD44 [32, 33]; the RGD and SVVYGLR sequences in OPN are responsible for its interaction with integrin [34], while CD44 binding sites in the OPN sequence have not yet been identified. Interestingly, OPN acts as a bridge molecule between CD44 variants and integrins to stimulate motility in murine cells [5].…”

Osteopontin Knockdown Inhibits av,�3Integrin-Induced Cell Migration and Invasion and Promotes Apoptosis of Breast Cancer Cells by Inducing Autophagy and Inactivating the PI3K/Akt/mTOR Pathway

“…A better understanding of the molecular basis of breast cancer is thus essential to improve the prognosis of this disease. Osteopontin (OPN) is a matricellular protein that binds to cell surface receptors, including integrins and CD44, resulting in a wide range of effects [2]. OPN plays important physiological roles in bone remodeling [3], the immune response [4] and inflammation [5].…”