Iduronic Acid in chondroitin/dermatan sulfate affects directional migration of aortic smooth muscle cells

Contains fulltext : 119303.pdf (publisher's version ) (Open Access)Aortic smooth muscle cells produce chondroitin/dermatan sulfate (CS/DS) proteoglycans that regulate extracellular matrix organization and cell behavior in normal and pathological conditions. A unique feature of CS/DS proteoglycans is the presence of iduronic acid (IdoA), catalyzed by two DS epimerases. Functional ablation of DS-epi1, the main epimerase in these cells, resulted in a major reduction of IdoA both on cell surface and in secreted CS/DS proteoglycans. Downregulation of IdoA led to delayed ability to re-populate wounded areas due to loss of directional persistence of migration. DS-epi1-/- aortic smooth muscle cells, however, had not lost the general property of migration showing even increased speed of movement compared to wild type cells. Where the cell membrane adheres to the substratum, stress fibers were denser whereas focal adhesion sites were fewer. Total cellular expression of focal adhesion kinase (FAK) and phospho-FAK (pFAK) was decreased in mutant cells compared to control cells. As many pathological conditions are dependent on migration, modulation of IdoA content may point to therapeutic strategies for diseases such as cancer and atherosclerosis

Polysaccharide Containing Gels for Pharmaceutical Applications

WOS: 000456875000007Bio-derived polymers are falling into the needs of pharmaceutical formulations for topical applications due to their gelling ability. Generally, in topical delivery, as an alternative way for local and systemic application of active substances, formulations in gelling form are preferred as they have multiple advantages, e.g., minimize systemic side effects, avoid gastrointestinal irritation, prevent the metabolism of the active substance in liver, etc. The present chapter reviews bio-based polymers with special reference to polysaccharides-based hydrogels with respect to their pharmaceutical applications