Sibalic V, Fan X, Loffing J, Wüthrich R P
Institute of Physiology, University of Zürich-Irchel, Switzerland.
Nephrol Dial Transplant. 1997 Jul;12(7):1344-53. doi: 10.1093/ndt/12.7.1344.
The hyaluronan (HA) receptor CD44 is upregulated on parenchymal cells in various inflammatory lesions and could play a role in immune injury. The purpose of the present study was to examine CD44 and its ligands HA and osteopontin (Opn) in a murine model of tubulointerstitial nephritis (TIN).
The expression of CD44 was investigated by immunofluorescence staining and RNA analysis in kidneys of kdkd mice with autoimmune TIN. The CD44 expression was then correlated with the location of its ligands HA and Opn.
CD44 is expressed de novo by tubular epithelial cells (TEC) in areas of tubular injury in kdkd kidneys, but not in normal control kidneys. CD44 positive lymphocytes and macrophages also infiltrate the kidney to kdkd mice. RT-PCR and Southern blot analysis demonstrate that transcripts encoding standard and variant forms of CD44 are increased in kdkd mice with TIN. In parallel the CD44 ligand HA also accumulates in kdkd kidneys in the interstitial space, particularly in cortical areas of tubular injury. Furthermore, the expression of the chemotactic protein Open is enhanced in kdkd kidney, predominantly in areas of tubular injury. Opn mRNA expression also increases markedly in kdkd kidneys compared with normal kidneys, and correlates with disease severity.
Prominent CD44 expression by TEC in areas of tubulointerstitial lesions is a characteristic feature of kdkd mice. The de novo appearance of CD44 on injured TEC might allow interaction with the ligands HA and Opn in vivo. Interaction of CD44 with these ligands could participate in the tubulointerstitial inflammatory response in kdkd mice.
透明质酸（HA）受体CD44在各种炎症病变的实质细胞上表达上调，可能在免疫损伤中起作用。本研究的目的是在肾小管间质性肾炎（TIN）的小鼠模型中检测CD44及其配体HA和骨桥蛋白（Opn）。
通过免疫荧光染色和RNA分析研究自身免疫性TIN的kdkd小鼠肾脏中CD44的表达。然后将CD44表达与其配体HA和Opn的定位相关联。
CD44在kdkd肾脏肾小管损伤区域的肾小管上皮细胞（TEC）中从头表达，但在正常对照肾脏中不表达。CD44阳性淋巴细胞和巨噬细胞也浸润kdkd小鼠的肾脏。RT-PCR和Southern印迹分析表明，编码CD44标准和变体形式的转录物在患有TIN的kdkd小鼠中增加。同时，CD44配体HA也在kdkd肾脏的间质空间中积聚，特别是在肾小管损伤的皮质区域。此外，趋化蛋白Opn在kdkd肾脏中的表达增强，主要在肾小管损伤区域。与正常肾脏相比，Opn mRNA在kdkd肾脏中的表达也明显增加，并且与疾病严重程度相关。
肾小管间质病变区域TEC中显著的CD44表达是kdkd小鼠的特征性表现。CD44在受损TEC上的从头出现可能允许其在体内与配体HA和Opn相互作用。CD44与这些配体的相互作用可能参与kdkd小鼠的肾小管间质炎症反应。
