Comparative proteomic analysis suggests that mitochondria are involved in autosomal recessive polycystic kidney disease.
Autosomal recessive polycystic kidney disease (ARPKD), characterized by ectatic collecting duct, is an infantile form of PKD occurring in 1 in 20 000 births. Despite having been studied for many years, little is known about the underlying mechanisms. In the current study, we employed, for the first time, a MS-based comparative proteomics approach to investigate the differently expressed proteins between kidney tissue samples of four ARPKD and five control individuals. Thirty two differently expressed proteins were identified and six of the identified protein encoding genes performed on an independent group (three ARPKD subjects, four control subjects) were verified by semi-quantitative RT-PCR, and part of them were further validated by Western blot and immunohistochemistry. Moreover, similar alteration tendency was detected after downregulation of PKHD1 by small interfering RNA in HEK293T cell. Interestingly, most of the identified proteins are associated with mitochondria. This implies that mitochondria may be implicated in ARPKD. Furthermore, the String software was utilized to investigate the biological association network, which is based on known and predicted protein interactions. In conclusion, our findings depicted a global understanding of ARPKD progression and provided a promising resource of targeting protein, and shed some light further investigation of ARPKD.
Core Facility of Genetically Engineered Mice, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Sichuan, People's Republic of China.
Qing-Wei
QW
Li
Xiao-Yan
XY
Lu
Yong
Y
You
Huan
H
Sun
Xin-Yu
XY
Liu
Jian-Zhong
JZ
Ai
Rui-Zhi
RZ
Tan
Tie-Lin
TL
Chen
Mian-Zhi
MZ
Chen
Hong-Lian
HL
Wang
Yu-Quan
YQ
Wei
Qin
Q
Zhou
D015153:Blotting, Western; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D017044:Polycystic Kidney, Autosomal Recessive / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D034741:RNA, Small Interfering / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D021241:Spectrometry, Mass, Electrospray Ionization
D024101:Mitochondrial Proteins; C451750:PKHD1 protein, human; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface