Declèves Anne-Emilie, Caron Nathalie, Nonclercq Denis, Legrand Alexandre, Toubeau Gérard, Kramp Ronald, Flamion Bruno
Molecular Physiology Research Unit (URPHYM), Laboratory of Physiology and Pharmacology, FUNDP - University of Namur, B-5000 Namur, Belgium.
Int J Mol Med. 2006 Jul;18(1):83-94.
Ischemia/reperfusion (I/R) injury in the kidney involves hemodynamic and cellular dysfunctions as well as leukocyte infiltration. Functional recovery occurs via cell proliferation and/or migration. To determine the roles of hyaluronan (HA) and its main receptor CD44 in renal postischemic processes, we compared their localization and expression with that of neutrophils, macrophages, and PCNA-positive (regenerative) cells as characterized by immunohistochemistry, up to 28 days after I/R in uninephrectomized rats. Observations covered all kidney zones, i.e. cortex (C), outer and inner stripes of outer medulla (OSOM, ISOM), and inner medulla (IM). In controls, HA was localized to the interstitium of IM and ISOM, and CD44 was mostly present on the basolateral membranes of collecting ducts in ISOM, the thin descending limb of Henle's loop and macula densa cells. After I/R, HA and CD44 staining appeared in C and OSOM at 12 h and persisted throughout the regenerative period, i.e. until day 7. Thereafter, they regressed but remained associated with remodeling areas. CD44 expression was found de novo on the apical pole of regenerating, not fully differentiated tubular cells and on some interstitial cells. It was prominent on all infiltrating neutrophils, as soon as 2 h post-I/R, and on 30% of the macrophages, including those in late HA-rich inflammatory granulomas. CD44 is probably involved in early leukocyte infiltration, in tubular regeneration, and in macrophage activity, while HA modifies the physico-chemical environment of interstitial and migrating cells. Based on its presence in remodeling areas, the HA-CD44 pair may be implicated in persistent postichemic inflammation as observed in chronic allograft nephropathy.
肾脏缺血/再灌注（I/R）损伤涉及血流动力学和细胞功能障碍以及白细胞浸润。功能恢复通过细胞增殖和/或迁移实现。为了确定透明质酸（HA）及其主要受体CD44在肾脏缺血后过程中的作用，我们通过免疫组织化学比较了它们与中性粒细胞、巨噬细胞和PCNA阳性（再生）细胞的定位和表达，观察时间长达单侧肾切除大鼠I/R后28天。观察覆盖了所有肾区，即皮质（C）、外髓质的外带和内带（OSOM、ISOM）以及内髓质（IM）。在对照组中，HA定位于IM和ISOM的间质，CD44主要存在于ISOM集合管的基底外侧膜、亨氏袢细降支和致密斑细胞上。I/R后，HA和CD44染色在12小时出现在C和OSOM，并在整个再生期持续存在，即直到第7天。此后，它们消退，但仍与重塑区域相关。在再生但未完全分化的肾小管细胞的顶端极和一些间质细胞上发现了CD44的从头表达。I/R后2小时，在所有浸润的中性粒细胞上以及30%的巨噬细胞上（包括那些富含HA的晚期炎性肉芽肿中的巨噬细胞），CD44表达显著。CD44可能参与早期白细胞浸润、肾小管再生和巨噬细胞活性，而HA改变间质和迁移细胞的物理化学环境。基于其在重塑区域的存在，HA-CD44对可能与慢性移植肾肾病中观察到的持续性缺血后炎症有关。
