Role of atrophic changes in proximal tubular cells in the peritubular deposition of type IV collagen in a rat renal ablation model
Role of atrophic changes in proximal tubular cells in the peritubular deposition of type IV collagen in a rat renal ablation model
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DOI：
10.1093/ndt/gfh872
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发表时间：
2005-08-01
影响因子：
6.1
通讯作者：
Hishida, A
中科院分区：
文献类型：
--
作者：
Kimura, M;Asano, M;Hishida, A
背景肾小管萎缩、扩张和间质纤维化在肾小管间质病变中很常见，但这些成分在间质病变发展中的确切作用和相互关系尚未确定。本研究重点关注大鼠肾消融模型中萎缩小管在IV型胶原管周沉积中的起源和作用。方法。雄性Wistar大鼠行5/6肾切除术或假手术，分别于术后4、8、12周处死，取剩余肾脏进行组织学、免疫组化及IV型胶原mRNA原位杂交研究。免疫组化显示萎缩小管波形蛋白、血小板源性生长因子B链（PDGF）和热休克蛋白47（HSP 47）阳性染色。对PDGF受体β、α-平滑肌肌动蛋白（α-SMA）和HSP 47中的一种或多种呈阳性的细胞聚集在萎缩小管周围。IV型胶原也增加了萎缩小管附近。这些亲密关系在马赛克管中得到了更清楚的证明，马赛克管由完整的和萎缩的近端肾小管上皮细胞组成，并且具有波形蛋白、血小板源性生长因子和热休克蛋白47的混合染色模式。间质细胞α-SMA或HSP 47阳性，或两者，与萎缩的，但不与完整的上皮细胞密切接触。IV型胶原只沉积在萎缩小管和HSP 47阳性间质细胞之间。IV型胶原mRNA的原位杂交结果显示其主要表达于萎缩的肾小管上皮细胞，而不表达于周围的间质细胞。这些发现表明，萎缩的近端小管细胞在小管周围空间中胶原沉积的发展中是活跃的，即在该模型中，间质纤维化区域中的IV型胶原可能主要由萎缩的近端小管产生。
Background. Tubular atrophy, dilation and interstitial fibrosis are common in tubulointerstitial lesions, but the precise roles and inter-relationships of these components in the development of interstitial lesions have not been determined. This study focused on the origin and roles of atrophic tubules in the peritubular deposition of type IV collagen in a rat renal ablation model.Methods. Male Wistar rats underwent 5/6 nephrectomy or sham operation, and then were sacrificed at 4 8 or 12 weeks, their remaining kidneys removed for histological and immuno-histochemical studies as well as in situ hybridization for type IV collagen mRNA.Results. Immuno-histochemistry demonstrated the positive staining of atrophic tubules to vimentin, platelet-derived growth factor-B chain (PDGF) and heat shock protein 47 (HSP47). Cells positive to one or more of PDGF receptor beta, alpha-smooth muscle actin (alpha-SMA), and HSP47 accumulated around atrophic tubules. Type IV collagen was also increased in the proximity of the atrophic tubules. These intimate relationships were more clearly demonstrated in,mosaic tubules', which are composed of both intact and atrophic proximal tubular epithelial cells, and which had a mixed pattern of staining with vimentin, PDGF and HSP47. The interstitial cells positive to alpha-SMA or HSP47, or both, were in close contact with atrophic but not with intact epithelial cells. Type IV collagen was exclusively deposited between atrophic tubules and HSP47-positive interstitial cells. In situ hybridization of type IV collagen mRNA demonstrated predominant expression in atrophic tubular epithelial cells, but not in surrounding interstitial cells.Conclusions. These findings suggest that atrophic proximal tubular cells are active in the development of collagen deposition in the peritubular space, i.e. in this model type IV collagen in the interstitial fibrotic area may be produced mainly by atrophic proximal tubules.