Extracellular Matrix Abnormalities in Major Psychoses: CS-6 Expression in Human Dermal Fibroblasts

Abstract

Emerging research on the extracellular matrix (ECM) has identified chondroitin sulfate proteoglycans (CSPGs) as one of the key contributors to abnormalities observed in major psychoses. This study aimed to explore expression of a specific form of sulfation, CS-6 (CS56), on chondroitin sulfate chains in dermal fibroblasts as an approach in understanding the role that ECM, and more specifically CSPGs, play in Schizophrenia and Bipolar Disorder. In this study, 39 human dermal fibroblast cell lines from normal controls, schizophrenic, and bipolar subjects were used. Cell lysates and conditioned media were collected at 24 and 72 hours to assess expression as well as secretion. Immunocytochemistry staining using anti-chondroitin sulfate anti-body CS-56 revealed that human dermal fibroblasts abundantly express CS56. Western Blot analyses showed no significant differences in CS-6 expression amongst the groups. Notably, significant changes were instead detected in olfactory mucosa cell lines from subjects with major psychoses, consistent with findings in the central nervous system. Together, these findings provide important clues on CSPG abnormalities in Schizophrenia and Bipolar Disorder, suggesting dysregulation exclusively in the nervous system.