Association of Asef and Cdc42 expression to tubular injury in diseased human kidney.
BACKGROUND
Cdc42 is a small guanosine-5'-triphosphatase of the Rho family and plays essential roles in the establishment of cellular polarity and tight junctions in epithelial cells. Adenomatous polyposis coli-associated exchange factor (Asef) is a canonical guanine nucleotide exchange factor of Cdc42 and renders Cdc42 to be guanosine-5'-triphosphate bound and activated. The expression patterns and their significance in human renal diseases are unknown.


METHODS
We examined the expression of Cdc42 and Asef in kidney biopsy specimens of 15 patients and in normal kidney tissue using immunofluorescence and correlated the expression patterns with the clinical characteristics. We also analyzed the coexpression pattern of Ki-67, a marker indicating cell division, and Asef in selected patients.


RESULTS
Expression of Asef and Cdc42 together was associated with tubular injury with 100% specificity. Expression of Asef, regardless of Cdc42, also showed a significant diagnostic odds ratio for the presence of the injury. Expression of Asef was associated with lower estimated glomerular filtration rate at the time of biopsy and larger area of interstitial fibrosis. All Ki-67-expressing tubular cells expressed Asef.


CONCLUSIONS
Induction of Asef and Cdc42 in the renal tubules is a cellular response to injury. Asef induction seems a necessary step for injured tubular cells to enter cell cycle.
From the Departments of *Internal Medicine and †Pathology, National Taiwan University Hospital Hsin-Chu Branch, Hsin Chu City, Taiwan; and ‡Institute ofMolecular and Cellular Biology, Department of Life Science, National Tsing Hua University, Hsin Chu City, Taiwan.
Hui-Teng
HT
Cheng
I Pu
IP
Juang
Liang-Chin
LC
Chen
Lih-Yuan
LY
Lin
Cheng-Han
CH
Chao
D000293:Adolescent; D000328:Adult; D000369:Aged, 80 and over; D005260:Female; D005786:Gene Expression Regulation; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007684:Kidney Tubules / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D064067:Rho Guanine Nucleotide Exchange Factors / Q000096:biosynthesis / Q000235:genetics; D055815:Young Adult; D020764:cdc42 GTP-Binding Protein / Q000096:biosynthesis* / Q000235:genetics
C576602:ARHGEF4 protein, human; D064067:Rho Guanine Nucleotide Exchange Factors; D020764:cdc42 GTP-Binding Protein