Nikolic-Paterson D J, Jun Z, Tesch G H, Lan H Y, Foti R, Atkins R C
Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia.
J Am Soc Nephrol. 1996 Jul;7(7):1006-14. doi: 10.1681/ASN.V771006.
CD44 is the major cell-surface receptor for hyaluronan, and cell-matrix interactions mediated by the CD44/hyaluronan receptor-ligand pair are involved in a variety of cellular functions, including cell migration. The aim of the study presented here was to examine the expression of CD44 and hyaluronan in the mesangial proliferative response in rat anti-Thy-1 nephritis. In normal rat kidney, CD44 is expressed by medullary tubules, some distal tubules and thick ascending limbs of Henle, dendritic-like cells around Bowman's capsule, and some interstitial cells. However, only occasional CD44+ cells were found within the glomerular tuft. In experimental nephritis, there was an early glomerular influx of CD44+ macrophages, which peaked on Day 4 after anti-Thy-1 antibody injection. A striking finding was de novo CD44 expression by mesangial cells. This CD44 expression was restricted to the transient period of mesangial cell proliferation as shown by double-staining with an antibody against the proliferating cell nuclear antigen. Immunohistochemistry staining also demonstrated hyaluronan deposition within segmental areas of proliferating CD44+ cells, suggesting a functional interaction between the CD44/hyaluronan receptor-ligand pair during mesangial cell proliferation. In vitro, rat mesangial cells were shown to express mRNA and protein for the 90-kd isoform of CD44. In addition, hyaluronan-dependent aggregation of CD44+ mesangial cells was specifically inhibited by an anti-CD44 antibody, demonstrating a functional interaction between hyaluronan and the CD44 expressed on the surface of rat mesangial cells. In conclusion, these data suggest that cell-matrix interactions mediated by the CD44/hyaluronan receptor-ligand pair are involved in mesangial cell proliferation in rat anti-Thy-1 nephritis.
CD44是透明质酸的主要细胞表面受体，由CD44/透明质酸受体-配体对介导的细胞-基质相互作用参与多种细胞功能，包括细胞迁移。本文所述研究的目的是检测CD44和透明质酸在大鼠抗Thy-1肾炎系膜增殖反应中的表达。在正常大鼠肾脏中，CD44由髓质肾小管、一些远端肾小管和亨利袢的厚升支、鲍曼囊周围的树突状细胞以及一些间质细胞表达。然而，在肾小球丛中仅偶尔发现CD44+细胞。在实验性肾炎中，早期有CD44+巨噬细胞流入肾小球，在注射抗Thy-1抗体后第4天达到峰值。一个显著的发现是系膜细胞从头表达CD44。如用抗增殖细胞核抗原抗体双重染色所示，这种CD44表达仅限于系膜细胞增殖的短暂时期。免疫组织化学染色还显示在增殖的CD44+细胞的节段区域内有透明质酸沉积，提示在系膜细胞增殖过程中CD44/透明质酸受体-配体对之间存在功能相互作用。在体外，大鼠系膜细胞显示表达CD44的90-kd异构体的mRNA和蛋白。此外，抗CD44抗体特异性抑制了CD44+系膜细胞的透明质酸依赖性聚集，证明透明质酸与大鼠系膜细胞表面表达的CD44之间存在功能相互作用。总之，这些数据表明由CD44/透明质酸受体-配体对介导的细胞-基质相互作用参与大鼠抗Thy-1肾炎的系膜细胞增殖。
