Differential MRNA Expression Of HGRβ And Splicing Factor SRp30c Is Associated With Gluocorticoid Sensitivity

Introduction Glucocorticoids ( GC) represent the cornerstone of anti-inflammatory treatment in many chronic inflammatory diseases. Although most patients respond to glucocorticoid, some patients fail to have a satisfactory response and are termed steroid-resistant. Steroid resistance was reported in many diseases such as asthma, chronic sinusitis, nephrotic syndrome, rheumatoid arthrites, systemic lupus erythematous, ulcerative colitis, atopic dermatitis,et al. It is more likely to be disease independent and poses a major clinical challenge. Delineation of the molecular basis for steroid resistance is critical for the development of new treatment approaches for this group of refractory patients, and may provide new insights into the pathogenesis of chronic inflammation.The pharmacologic actions of GCs are mediated through intracellular receptors, the glucocorticoid receptors(hGR). There are two isoforms of hGR in human cells, hGR α and hGRβ . which are generated from a single gene via alternative splicing of the primary RNA trascript. hGR P can't bind GC and does not transactivate GC sensitive genes. It functions as a dominant inhibitor of hGR α . Several studied indicate that steroid resistance has been associated with increased expression of hGRβ . Recently it was reported that the member of serine/arginine-rich proteins SRp30c is necessary for alternative splicing of the hGR pre-mRNA to create mRNA encoding hGRβ .So upregulation of splicing factor SRp30c might stimulate the expression of hGR β by alternative splicing in steroid resistant patients.Objective To clarify the relationship between the expression of human glucocorticoid...