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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1446672
This article is part of the Research Topic Immunological Aspects of Fibrosis Pathogenesis: Novel Mechanisms and Therapeutic Strategies View all 7 articles

Targeting AXL cellular networks in kidney fibrosis

Provisionally accepted
Sturla M. Grøndal Sturla M. Grøndal 1*Magnus Blø Magnus Blø 2*Linn H. Nilsson Linn H. Nilsson 2Austin J. Rayford Austin J. Rayford 1,2*Akil Jackson Akil Jackson 3Gro Gausdal Gro Gausdal 2James Lorens James Lorens 1*
  • 1 University of Bergen, Bergen, Norway
  • 2 BerGenBio (Norway), Bergen, Hordaland, Norway
  • 3 Bergenbio Ltd., Oxford, United Kingdom

The final, formatted version of the article will be published soon.

    The incidence of chronic kidney disease (CKD) is increasing, in parallel with risk factors including obesity and diabetes mellitus. AXL plays a central role in CKD, providing a rationale to evaluate clinical AXL targeting agents. To determine the efficacy and underlying molecular mechanisms of AXL inhibition in CKD, we employed a murine unilateral ureteral obstruction (UUO) model treated with a selective AXL kinase inhibitor (bemcentinib) during disease progression. Preventive treatment with bemcentinib significantly attenuated fibrosis in the UUO model. The anti-fibrotic effect correlated with a decrease in mesangial cells and inhibition of innate immune cell infiltration, while the proportion of epithelial cells increased. We mapped AXL expression to a unique network of cells in the kidney: mesangial cells, pericytes, macrophages and dendritic cells. We propose that AXL targeting affects an important cellular interaction network underlying fibrotic progression. These results support the clinical application of AXL targeting agents to treat CKD.

    Keywords: Axl, Bemcentinib, UUO (unilateral ureteral obstruction), Mass cytometry (CyTOF), Fibrosis, Inflammation

    Received: 10 Jun 2024; Accepted: 14 Oct 2024.

    Copyright: © 2024 Grøndal, Blø, Nilsson, Rayford, Jackson, Gausdal and Lorens. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Sturla M. Grøndal, University of Bergen, Bergen, Norway
    Magnus Blø, BerGenBio (Norway), Bergen, Hordaland, Norway
    Austin J. Rayford, BerGenBio (Norway), Bergen, Hordaland, Norway
    James Lorens, University of Bergen, Bergen, Norway

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.