Stem cell marker TRA-1-60 is expressed in foetal and adult kidney and upregulated in tubulo-interstitial disease.
The kidney has an intrinsic ability to repair itself when injured. Epithelial cells of distal tubules may participate in regeneration. Stem cell marker, TRA-1-60 is linked to pluripotency in human embryonic stem cells and is lost upon differentiation. TRA-1-60 expression was mapped and quantified in serial sections of human foetal, adult and diseased kidneys. In 8- to 10-week human foetal kidney, the epitope was abundantly expressed on ureteric bud and structures derived therefrom including collecting duct epithelium. In adult kidney inner medulla/papilla, comparisons with reactivity to epithelial membrane antigen, aquaporin-2 and Tamm-Horsfall protein, confirmed extensive expression of TRA-1-60 in cells lining collecting ducts and thin limb of the loop of Henle, which may be significant since the papillae were proposed to harbour slow cycling cells involved in kidney homeostasis and repair. In the outer medulla and cortex there was rare, sporadic expression in tubular cells of the collecting ducts and nephron, with positive cells confined to the thin limb and thick ascending limb and distal convoluted tubules. Remarkably, in cortex displaying tubulo-interstitial injury, there was a dramatic increase in number of TRA-1-60 expressing individual cells and in small groups of cells in distal tubules. Dual staining showed that TRA-1-60 positive cells co-expressed Pax-2 and Ki-67, markers of tubular regeneration. Given the localization in foetal kidney and the distribution patterns in adults, it is tempting to speculate that TRA-1-60 may identify a population of cells contributing to repair of distal tubules in adult kidney.
Fesenko
Irina
I
Infection, Inflammation and Immunity Division, School of Medicine, University of Southampton, Southampton, UK.
Franklin
Danielle
D
Garnett
Paul
P
Bass
Paul
P
Campbell
Sara
S
Hardyman
Michelle
M
Wilson
David
D
Hanley
Neil
N
Collins
Jane
J
D000328:Adult; D000368:Aged; D000954:Antigens, Surface / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D007668:Kidney / Q000196:embryology* / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology; D007679:Kidney Medulla / Q000196:embryology / Q000378:metabolism; D007686:Kidney Tubules, Distal / Q000196:embryology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000378:metabolism* / Q000473:pathology; D009399:Nephrons / Q000196:embryology / Q000378:metabolism; D051762:PAX2 Transcription Factor / Q000378:metabolism; D039904:Pluripotent Stem Cells; D011509:Proteoglycans / Q000378:metabolism*; D012038:Regeneration; D013234:Stem Cells / Q000378:metabolism*; D015854:Up-Regulation
D000954:Antigens, Surface; D015415:Biomarkers; D019394:Ki-67 Antigen; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D011509:Proteoglycans; C107064:TRA-1-60 antigen, human