Deficiency of either P-glycoprotein or breast cancer resistance protein protect against acute kidney injury
Authors: Gerard F M Merkx
Catherine M Verfaillie
Aernout Luttun
Rob M Woestenenk
Frans G M Russel
Lars R van Bolderen
Jack F M Wetzels
Rosalinde Masereeuw
Miriam Huls
Fernando Ulloa-Montoya
Aswin L Menke
Joost P H Schoeber
Journal: Cell transplantation (2010)
Discipline: CLINICAL MEDICINE
Keywords: kidney regeneration; ischemic injury; bone marrow-derived cells; ATP binding cassette transporters; P-glycoprotein
Affiliations: Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands., Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Abstract:  The kidney has a high capacity to regenerate after ischemic injury via several mechanisms, one of which involves bone marrow-derived (stem) cells. The ATP binding cassette transporters, P-glycoprotein and breast cancer resistance protein, are determinants for the enriched stem and progenitor cell fraction in bone marrow. Because they are upregulated after acute kidney injury, we hypothesized that both efflux pumps may play a role in protecting against renal injury. Surprisingly, transporter-deficient mice were protected against ischemia-induced renal injury. To further study this, bone marrow from irradiated wild-type mice was reconstituted by bone marrow from wild-type, P-glycoprotein- or breast cancer resistance protein-deficient mice. Four weeks later, kidney injury was induced and its function evaluated. Significantly more bone marrow-derived cells were detected in kidneys grafted with transporter-deficient bone marrow. A gender mismatch study suggested that cell fusion of resident tubular cells with bone marrow cells was unlikely. Renal function analyses indicated an absence of renal damage following ischemia-reperfusion in animals transplanted with transporter-deficient bone marrow. When wild-type bone marrow was transplanted in breast cancer resistance protein-deficient mice this protection is lost. Furthermore, we demonstrate that transporter-deficient bone marrow contained significantly more monocytes, granulocytes, and early outgrowth endothelial progenitor cells. 

Retracted: No

PubPeer comments:
 Figure 1 and 2. * Red boxes: The baseline bcrp- - panel looks unexpectedly similar to the BCRP-WT 2 days after injury panel, albeit with a different aspect ratio. Could the authors please check?  , 
 Figure 4A. * Light blue: the P-gp-WT mouse at baseline appears to show an overlap with the BCRP-WT mouse at baseline * Yellow: the P-gp-WT mouse at 7 days appears to show an overlap with the BCRP-WT mouse at baseline; the similarities are only in the red channel, not in the green channel * Magenta: theBCRP-WT mouse at 2 days appears to show an overlap with the BCRP-WT mouse at 7 days; the similarities are mostly in the red channel, while the signal in the green channel appears very different Could the authors please explain what happened here?  , 
 Figure 2B: Several panels appear to look similar to panels in an older paper by the same research group. That paper is Huls et al. 2007, Kidney International, doi:10.1038 sj.ki.5002522. * In lime green: the 2007 WT 2 days mouse looks similar to the 2010 WT-WT 2 days mouse. Note that in the 2007 paper a wild type FVB mouse was used, while the 2010 photo represents a WT mouse that was transplanted with WT tissue ( WT-WT ). So the photos do not appear to represent the same experiments. * In blue: the 2007 WT 7 days mouse looks similar to the 2010 WT-WT 7 days mouse. * In orange: the 2007 mdr1a 1b baseline mouse looks similar to the 2010 P-gp-WT 7 days mouse. Could the authors please check which mice these photos should represent?  , 
 Retraction, 26 September 2021: https: journals.sagepub.com doi 10.1177 09636897211031022  The retraction follows an investigation by the Radboud University Medical Center and the Journalu2019s Editorial team. That investigation found that Figures 1B (Panel d) and 2B (Panel h) appear to be identical, despite having different meanings in the paper. Three panels of Figure 2B were taken from Figure 8 of another paper by the group published in Kidney International in 2007. Figure 4A also appears to contain identical panels (d-g, f-g and h-i). The investigation found no primary actor responsible for the possible honest errors or manipulation of the figures. Due to the multiple, serious issues identified with the above-referenced figures, the journal has determined to retract the article. The authors were not able to provide an explanation for the problems identified with the figures. They support the decision to retract the article, while expressing their view that these issues did not affect the major conclusions. The authors apologize for any inconvenience this may have caused. I thank the journal, publisher, and institution for this investigation. Reported to journal: December 2019. ,