Localization and Roles of CD44, Hyaluronic Acid and Osteopontin in IgA Nephropathy

Abstract

An important function of CD44 is to act as a cellular receptor for hyaluronic acid and osteopontin. Cell-matrix interactions mediated by the CD44/hyaluronic acid receptor-ligand pair are involved in the regulation of leukocyte migration and activation. Osteopontin is a molecule associated with cell adhesion and migration and functions through binding to CD44. This study examined whether CD44, hyaluronic acid and osteopontin participate in the progression of IgA nephropathy. CD44 was expressed in mesangial cells, crescents, tubular cells and interstitial infiltrating cells in areas of tubulointerstitial injury. Hyaluronic acid was deposited in the capillary tuft of adhesion, crescents and the periglomerular area, and around damaged tubules. Osteopontin was expressed in tubular cells and interstitial infiltrating cells in areas of tubulointerstitial injury. The glomerular and interstitial deposition of hyaluronic acid correlated with the glomerular and interstitial expression of CD44. The interstitial expression of CD44 correlated with the interstitial expression of osteopontin. The expression of both CD44 and osteopontin in the interstitium correlated with the extent of tubulointerstitial damage. The expression of CD44 in the interstitium correlated with the severity of chronic glomerular lesions. The glomerular and interstitial CD44 and hyaluronic acid expression correlated with proteinuria, and interstitial CD44 and hyaluronic acid expression correlated with creatinine clearance rate. In summary, this study suggests that CD44 participates in the progression of IgA nephropathy by binding hyaluronic acid and osteopontin.

Progression of Diabetic Nephropathy Enhances the Plasma Osteopontin Level in Type 2 Diabetic Patients

“…In contrast, another participant at the stage of macroalbuminuria, whose plasma OPN levels reached 1,372 ng/ml, had been histologically diagnosed with diabetic nephropathy with membranous nephritis by renal biopsy. Since several investigators have recently shown that OPN could participate in the formation and progression of autoimmune and experimental nephritis [24][25][26][27], it is plausible to assume that a patient with an extremely high plasma OPN level, but not at the stage of renal failure, should be advised to have a renal biopsy to diagnose additional nephritis. Although the reason why the plasma OPN level was elevated only in the progression of nephropathy but not in that of retinopathy remains unclear, it is reasonable to assume that the plasma OPN level in the whole body might result from the size of each organ itself, and that the OPN level in the retinal tissue could be locally increased.…”

Sp1 and Sp3 Mediate Constitutive Transcription of the Human Hyaluronan Synthase 2 Gene

“…Following acute ischemic injury, interstitial inflammation, or during progressive renal fibrosis, however, there is greatly increased peritubular expression of both HA and the cell surface HA receptor CD44 in the cortex (23)(24)(25)(26)(27)(28). This suggests that alterations in HA synthesis and turnover may be involved either in the maintenance of homeostasis or in the development of pathological events, but the role of HA remains unclear.…”

Overexpression of c-Met and CD44v6 Receptors Contributes to Autocrine TGF-β1 Signaling in Interstitial Lung Disease

“…Increased deposition of interstitial HA has also been correlated with tissue function in progressive fibrosis, including ILD (12,13,23). Progressive ILD requires the generation of an invasive myofibroblast phenotype that requires TGF-␤1, where hyaluronan synthase 2 and CD44 are critical downstream components of TGF-␤1-induced fibrosis (14).…”