Splicing alterations in human renal allografts: detection of a new splice variant of protein kinase Par1/Emk1 whose expression is associated with an increase of inflammation in protocol biopsies of tr
详细信息 查看全文
- 作者：Hueso ; Miguel ; Beltran ; Violeta ; Moreso ; Francesc ; Ciriero ; Eva ; Fulladosa ; Xavier ; Grinyó ; Josep Maria ; et. al.
- 关键词：Kidney allograft ; Banff 97 schema ; Protocol biopsy ; Chronic allograft nephropathy (CAN) ; ser/thr protein kinase Par1/Emk1 ; Splicing alteration ; Cryptic exon
- 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Basis of Disease
- 出版年：2004
- 出版时间：May 24, 2004
- 年：2004
- 卷：1689
- 期：1
- 页码：58-65
- 全文大小：257 K
文摘
Protein kinase Emk1/Par1 (GenBank accession no. X97630) has been identified as a regulator of the immune system homeostasis. Since immunological factors are critical for the development of chronic allograft nephropathy (CAN), we reasoned that expression of Par1/Emk1 could be altered in kidney allografts undergoing CAN. In this paper, we have analysed the association among renal allograft lesions and expression of Par1/Emk1, studied by RT-PCR on total RNA from 51 protocol biopsies of transplanted kidneys, five normal kidneys, and five dysfunctional allografts. The most significant result obtained has been the detection of alterations in the normal pattern of alternative splicing of the Par1/Emk1 transcript, alterations that included loss of expression of constitutively expressed isoforms, and the inclusion of a cryptic exon to generate a new Emk1 isoform (Emk1C). Expression of Emk1C was associated with an increase in the extension of the interstitial infiltrate (0.88±0.33 in Emk1C[+] vs. 0.41±0.50 in Emk1C[−]; P<0.011), and with a trend to display higher interstitial scarring (0.66±0.70 vs. 0.29±0.52; P