title: Podocyte injury damages other podocytes.
abstract: Loss of podocytes promotes glomerulosclerosis, but whether this results from a continued primary insult or a secondary mechanism triggered by the initial loss of podocytes is unknown. We generated chimeric mice in which only a subpopulation of podocytes expressed hCD25, which is the receptor for the immunotoxin LMB2. In addition, genetic labeling of hCD25-negative cells with human placental alkaline phosphatase allowed the study of these two distinct podocyte populations. Administration of LMB2 did not cause podocyte injury in hCD25-negative control mice. In contrast, LMB2 severely damaged or sloughed off the subpopulation of hCD25-positive podocytes within the chimeric glomeruli. Moreover, hCD25-negative podocytes, which were immune to the initial toxin injury, developed injury as early as 4 d after LMB2 injection, evidenced by foot process effacement, upregulation of desmin, and downregulation of nephrin, podocin, and podocalyxin. Furthermore, the magnitude of secondary injury correlated with the magnitude of primary injury, supporting the concept of an amplified cascade of podocyte injury. In conclusion, podocyte damage can propagate injury by triggering secondary damage of "remnant" intact podocytes, even when the primary insult is short-lived. This transmission of podocyte injury may form a vicious cycle leading to accelerated podocyte deterioration and glomerulosclerosis.
authors: Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors: Taiji
authors: T
authors: Matsusaka
authors: Eric
authors: E
authors: Sandgren
authors: Ayumi
authors: A
authors: Shintani
authors: Valentina
authors: V
authors: Kon
authors: Ira
authors: I
authors: Pastan
authors: Agnes B
authors: AB
authors: Fogo
authors: Iekuni
authors: I
authors: Ichikawa
mesh_terms: D000818:Animals; D046528:Chimerism; D005260:Female; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009400:Nephrosclerosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D050199:Podocytes / Q000473:pathology* / Q000502:physiology; D019076:Transgenes
chemical_list: C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit