Structural analysis of how podocytes detach from the glomerular basement membrane under hypertrophic stress.

Structural analysis of how podocytes detach from the glomerular basement membrane under hypertrophic stress.
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DOI:
10.3389/fendo.2014.00207
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发表时间:
2014
影响因子:
5.2
通讯作者:
Waldherr R
Waldherr R
中科院分区:
医学2区
文献类型:
--
作者:
Kriz W;Hähnel B;Hosser H;Rösener S;Waldherr R

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足细胞作为活细胞从GBM脱离而丢失;细节在很大程度上是未知的。我们研究了这个过程中的大鼠生长刺激后,FGF-2。内皮细胞和系膜细胞通过增生反应,足细胞经历肥大,但是,从长远来看,发展出各种变化,这些变化可以被解释为显示从GBM脱离的进展阶段或通过足突消失(FPE)导致更紧密附着的阶段。这发生在同一足细胞内的微区;因此,分离和增强附着的特征可以同时在同一足细胞中发现。(1)最初,肥大的足细胞经历细胞体衰减并形成大的假囊肿,即,足细胞下空间的扩张。(2)足细胞进入FPE过程,开始于足突(FP)的回缩和通过闭塞连接替换狭缝隔膜,从而密封过滤狭缝。该过程的成功完成导致足细胞细胞体广泛附着于GBM。(3)密封狭缝的失败导致收缩FP之间的不同宽度的间隙,促进滤液从GBM流出。(4)由于这些间隙经常被增宽的初级突起覆盖,滤液排入Bowman间隙可能会受到阻碍,导致与GBM裸露区域相关的小假性囊肿形成。(5)假性囊肿的合并创造了一个连通腔室系统,滤液必须通过该系统才能到达鲍曼氏腔。串联的多个流动阻力可能在足细胞上产生有助于分离的膨胀力。(6)这种情况似乎进行到一组足细胞由于它们之间的交界连接而通常完全断开。(7)由于这些分离的足细胞群通常与壁细胞接触,它们开始形成与鲍曼氏囊的簇粘连。
Podocytes are lost by detachment from the GBM as viable cells; details are largely unknown. We studied this process in the rat after growth stimulation with FGF-2. Endothelial and mesangial cells responded by hyperplasia, podocytes underwent hypertrophy, but, in the long run, developed various changes that could either be interpreted showing progressing stages in detachment from the GBM or stages leading to a tighter attachment by foot process effacement (FPE). This occurred in microdomains within the same podocyte; thus, features of detachment and of reinforced attachment may simultaneously be found in the same podocyte. (1) Initially, hypertrophied podocytes underwent cell body attenuation and formed large pseudocysts, i.e., expansions of the subpodocyte space. (2) Podocytes entered the process of FPE starting with the retraction of foot processes (FPs) and the replacement of the slit diaphragm by occluding junctions, thereby sealing the filtration slits. Successful completion of this process led to broad attachments of podocyte cell bodies to the GBM. (3) Failure of sealing the slits led to gaps of varying width between retracting FPs facilitating the outflow of the filtrate from the GBM. (4) Since those gaps are frequently overarched by broadened primary processes, the drainage of the filtrate into the Bowman’s space may be hindered leading to the formation of small pseudocysts associated with bare areas of GBM. (5) The merging of pseudocysts created a system of communicating chambers through which the filtrate has to pass to reach Bowman’s space. Multiple flow resistances in series likely generated an expansile force on podocytes contributing to detachment. (6) Such a situation appears to proceed to complete disconnection generally of a group of podocytes owing to the junctional connections between them. (7) Since such groups of detaching podocytes generally make contact to parietal cells, they start the formation of tuft adhesions to Bowman’s capsule.
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