Immuno-Localization of CD44 and Osteopontin in Developing Human Kidney

Abstract

CD44 is observed in ureteric bud structures and is implicated in branching morphogenesis during early mouse renal development. Healthy adult kidney demonstrates minimal CD44, but CD44 is up-regulated in renal diseases. CD44 may mediate binding of calcium oxalate crystals to tubular epithelia via the ligands osteopontin (OPN) and hyaluronan. Because 15% of premature infants develop nephrocalcinosis, developmental tubular CD44 expression might promote nephrocalcinosis. We studied CD44 and OPN immuno-localization in developing human kidney by immunohistochemical analysis. Human renal tissue between 18 and 40 wk of gestation showed CD44 immuno-localization in ureteric buds, with staining decreasing with increasing gestational age; CD44 was rarely observed in developing renal tubules. OPN was diffusely observed in proximal tubules, rarely observed in distal tubules, ureteric buds or metanephric structures. These data support the role of CD44 in early human nephron formation and branching morphogenesis. Rare CD44 staining in developing tubular epithelium suggests no role for CD44 in promoting calcium oxalate adherence to tubular epithelia in premature infants. Immuno-localization of OPN in tubules supports its role in tubular differentiation, but OPN does not seem to be necessary during early nephron formation. (Pediatr Res 65: 79-84, 2009) P remature birth imposes considerable stress on the kidney during a critical period of nephron formation and differentiation. Consequences of this stress include nephrocalcinosis, which has been reported to occur in approximately 15% of premature infants and may be associated with impaired renal function in later childhood (1-4). Decreased nephron mass in young adults who were born prematurely is associated with hypertension and impaired renal function (5). Studies of mammalian nephrogenesis have identified transcription factors, growth factors, and signaling proteins, which control the complex series of interactions resulting in kidney formation. Some factors that play a role in nephrogenesis can be reexpressed in adulthood during renal injury and may play a role in progressive renal damage (6). Although many of the basic mechanisms of nephrogenesis have been elucidated, there is very little information regarding immuno-localization of these factors in the developing human kidney.CD44 is a cell surface glycoprotein receptor and adhesion molecule which is expressed in many human cell types and has been implicated in a variety of physiologic and pathologic processes including lymphocyte homing, wound healing, cell migration, and tumor growth and metastasis (7-10). CD44 in normal mature human kidney is limited to endothelial cells, interstitial cells, and circulating leukocytes. However, upregulation of CD44 in tubular and glomerular epithelia because of renal injury has been observed in both human kidney disease and animal models of renal injury (11-16). CD44 is observed during renal embryogenesis at the ureteric bud, where reciprocal interaction of CD44 with hyaluronan (H...

The developmental programme for genesis of the entire kidney is recapitulated in Wilms tumour

“…WT1 is highly expressed in early metanephrogenic epithelial structures in fetal kidneys, while its expression is absent in the UB of the developing kidney [ 4 ]. Meanwhile, MUC-1 is known to be expressed in the UB of the developing kidney [ 22 , 40 ], which was differentially expressed in the triphasic tumours in our microarray data. We examined whether the WT1-negative and MUC-1 positive (WT1 - /MUC-1 + ) epithelial structures ( Fig 4B , S5A and S5B Fig ) in WTs are equivalent to the UB of the developing kidney.…”

Immunolocalization of the calcium-sensing receptor in developing human kidney

“…Immunohistochemical staining was performed on a DakoCytomation AutoStainer using the Dako ADVANCE HRP/DAB staining kit protocol in accordance with the Signet Acuity data sheet (Dako, Carpenteria, CA), as previously reported (32). The antibodies used included mouse monoclonal antibody anti-CSR clone 5C10 corresponding to amino acids 214-235 of the human CSR (1:10,000; Novus Biologicals, Littleton, CO) (33), rabbit polyclonal antibody anti-CSR corresponding to amino acids 345-359 of the bovine CSR (1:500, generous gift of Edward M. Brown) (34), monoclonal antihuman EMA clone E29 (1:4,000; Dako) (35), monoclonal CD10 clone 56C6 (1:200; Vector Laboratories, Burlingame, CA) (36), and polyclonal antibody to PAX2 (1:100; Invitrogen, Camarillo, CA) (37).…”

Kidney‐in‐a‐lymph node: A novel organogenesis assay to model human renal development and test nephron progenitor cell fates

“…Indeed, our experience suggests long‐term retention of the glomeruli while the renal tubules (especially the distal segments) are progressively lost. This phenomenon is not due to fibrosis or the conversion of the LN into a fibrotic environment, as suggested by staining for Erasmus University Rotterdam‐Thymic Reticulum (ER‐TR7), CD44, and platelet‐derived growth factor receptor beta (PDGFR‐β; Figure S4), which are expressed in kidney during development and/or adult life (Crisi, Marconi, Rockwell, Braden, & Campfield, ; Floege et al, ; Tsujie et al, ), and overexpressed during renal disease (Floege, Eitner, & Alpers, ; Kirimca, Sarioglu, Camsari, & Kavukcu, ; Roy‐Chaudhury et al, ; Wagrowska‐Danilewicz & Danilewicz, ). The precise mechanism of tubular loss in our ectopic human kidney grafts remains unknown.…”