Expression of mRNA for type IV collagen alpha1, alpha5 and alpha6 chains by cultured dermal fibroblasts from patients with X-linked Alport syndrome.
Expression of mRNA for type IV collagen alpha1, alpha5 and alpha6 chains by cultured dermal fibroblasts from patients with X-linked Alport syndrome.
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X 连锁 Alport 综合征患者培养的真皮成纤维细胞表达 IV 型胶原 α1、α5 和 α6 链 mRNA。
DOI：
10.1016/s0945-053x(98)90081-6
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Kashtan,CE
中科院分区：
文献类型：
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作者：
Sasaki,S;Zhou,B;Fan,WW;Kim,Y;Barker,DF;Denison,JC;Atkin,CL;Gregory,MC;Zhou,J;Segal,Y;Sado,Y;Ninomiya,Y;Michael,AF;Kashtan,CE
导致X连锁Alport综合征（XLAS）的COL 4A 5突变通常与基底膜中IV型胶原α3、α4、α5和α6链缺失以及肾小球基底膜中α1（IV）和α2（IV）链数量增加相关。尽管XLAS中描述了许多COL 4A 5突变，但这些突变影响α5（IV）以外链的基底膜外观的机制仍知之甚少。在这项研究中，我们使用来自8名正常人和9名XLAS男性的皮肤成纤维细胞来测试COL 4A 5突变增加COL 4A 1转录和抑制COL 4A 6转录的假设。核糖核酸酶保护试验表明，α1（IV），α5（IV）和α6（IV）的转录表达在培养的真皮成纤维细胞。与对照组相比，8例9例XLAS患者的α1（IV）mRNA水平未升高; 1例COL 4A 5大缺失患者的α1（IV）mRNA水平显著升高。当XLAS成纤维细胞与对照相比时，未发现α6（IV）的稳态mRNA水平存在差异，即使通过免疫荧光研究在真皮-表皮交界处检测到很少或没有α6（IV）蛋白。这一发现表明，转录后事件解释了Alport真皮-表皮连接中α6（IV）的缺失。
COL4A5 mutations causing X-linked Alport syndrome (XLAS) are frequently associated with absence of the α3, α4, α5 and α6 chains of type IV collagen from basement membranes and increased amounts of the α1(IV) and α2(IV) chains in glomerular basement membrane. Although many COL4A5 mutations have been described in XLAS, the mechanisms by which these mutations influence the basement membrane appearance of chains other than α5(IV) remain poorly understood. In this study, we used dermal fibroblasts from eight normal individuals and nine males with XLAS to test the hypotheses that COL4A5 mutations increase transcription of COL4A1 and suppress transcription of COL4A6. Ribonuclease protection assays revealed that α1(IV), α5(IV) and α6(IV) transcripts were expressed in cultures of dermal fibroblasts. The mRNA levels for α1(IV) in eight nine patients with XLAS were not increased compared to controls; one patient with a large COL4A5 deletion showed significant elevation of α1(IV) mRNA levels. No differences in steady-state mRNA levels for α6(IV) were found when XLAS fibroblasts were compared with controls, even though little or no α6(IV) protein was detectable at the dermal-epidermal junction by immunofluorescence study. This finding suggests that post-transcriptional events account for the absence of α6(IV) in the Alport dermal-epidermal junction.