title: Microchimeric fetal cells are recruited to maternal kidney following injury and activate collagen type I transcription.
abstract: Fetal cells enter the maternal circulation from the early first trimester of pregnancy, where they persist in tissue decades later. We investigated in mice whether fetal microchimeric cells (FMCs) can be detected in maternal kidney, and whether they play a role in kidney homeostasis. FMCs were identified in vivo in two models: one an adaptive model following unilateral nephrectomy, the other an injury via unilateral renal ischaemia reperfusion. Both models were carried out in mothers that had been mated with transgenic mice expressing luciferase transgene under the control of collagen type I, and had given birth to either 1 or 3 litters. FMCs were detected by Y-probe fluorescent in situ hybridization (FISH) and bioluminescence, and the cell number quantified by real-time polymerase chain reaction. In the adaptive model, the remaining kidney showed more cells by all 3 parameters compared with the nephrectomized kidney, while ischaemia reperfusion resulted in higher levels of FMC participation in injured compared to contralateral kidneys. Bioluminescence showed that FMCs switch on collagen type I transcription implicating mesenchymal lineage cells. After injury, Y-probe in situ hydridization was found mainly in the tubular epithelial network. Finally, we compared FMCs with bone marrow cells and found similar dynamics but altered distribution within the kidney. We conclude that FMCs (1) are long-term sequelae of pregnancy and (2) are recruited to the kidney as a result of injury or adaptation, where they activate the transcriptional machinery of matrix proteins.
authors.affiliation: Kennedy Institute of Rheumatology, Imperial College London, Hammersmith Campus, London, UK.
authors.forename: George
authors.initials: G
authors.lastname: Bou-Gharios
authors.forename: Farhana
authors.initials: F
authors.lastname: Amin
authors.forename: Peter
authors.initials: P
authors.lastname: Hill
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Patrick
authors.initials: P
authors.lastname: Maxwell
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Fisk
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002452:Cell Count; D002465:Cell Movement / Q000235:genetics; D046528:Chimerism / Q000196:embryology*; D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000166:cytology*; D017404:In Situ Hybridization, Fluorescence; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D008156:Luciferases / Q000378:metabolism; D008163:Luminescent Measurements; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D019076:Transgenes / Q000235:genetics; D014945:Wound Healing / Q000235:genetics; D014998:Y Chromosome / Q000235:genetics; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D008156:Luciferases; D001616:beta-Galactosidase