Tubular epithelial cells have the capacity to transdifferentiate into CD68-positive macrophage-like cells by oxidative stress.
OBJECTIVE
The present study was intended to assess transdifferentiation from tubular epithelial cells to macrophage- like cells.


METHODS
Puromycin aminonucleoside nephrotic rats were sacrificed at days 4, 8, 24 and 112. We immunohistochemically evaluated CD68, CD163, and cytokeratin AE1/AE3, known as markers for macrophages and tubular epithelial cells. Nitrotyrosine, gp91(phox) and Rac 1 expressions was also analyzed. CD68 expression in cultured murine proximal tubular epithelial cells (mProx) stimulated by crude and pure BSA was examined by flow cytometry and immunofluorescence.


RESULTS
The tubular CD68-positive cells were observed on day 112. Immunoelectronmicroscopy revealed that some CD68-positive cells showed brush borders on the cell membrane and some of cytokeratin-positive tubular cells also expressed CD163 in mirror sections. The tubular CD68-positive cells were also positive for nitrotyrosine, gp91 (phox) and Rac 1. They contained lipid in their cytoplasm. Crude BSA, containing free fatty acid, induced CD68 expression in a dose- and time-dependent manner in mProx, but not pure BSA. The surface expression of CD68 was increased by high dose and long term stimulation with crude BSA as shown by immunofluorescence.


CONCLUSIONS
We confirmed that tubular epithelial cells have the capacity to transdifferentiate to CD68-positive macrophage-like cells, which may be linked to oxidative stress.
Tanaka
M
M
Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Suzuki
Y
Y
Shirato
I
I
Takahara
H
H
Shibata
T
T
Sugaya
T
T
Shimamoto
K
K
Horikoshi
S
S
Tomino
Y
Y
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D054338:Cell Transdifferentiation / Q000502:physiology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D007633:Keratins / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology*; D050356:Lipid Metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism; D014556:Urine / Q000737:chemistry; D000098902:CD163 Antigen; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D007633:Keratins; D011956:Receptors, Cell Surface; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule