Abstract
IL-22, a member of the IL-10 cytokine family, accelerates tubule regeneration upon acute kidney injury, hence we speculated on a protective role also in chronic kidney disease. We quantified intrarenal IL-22 expression after unilateral ureteral (UUO) in wild-type mice and performed UUO in IL-22 knock-out animals. Obstruction phenotypic differences between IL22(+/+) and IL22(-/-) mice were assessed by histology, immunohistochemistry, immunofluorescence as well as western blotting and reverse-transcriptase quantitative PCR ex vivo. Additionally, we performed in vitro experiments using both murine and human tubular cells to characterize IL-22 effects in epithelial healing. We found increasing IL22 positivity in infiltrating immune cells over time upon UUO in wild-type mice. UUO in IL22(-/-) mice caused more tubular cell injury as defined by TUNEL positive cells and loss of tetragonolobus lectin staining. Instead, tubular dilation, loss of CD31+ perivascular capillaries, and interstitial fibrosis were independent of the Il22 genotype as assessed by standard histology, immunostaining, and mRNA expression profiling. In vitro experiments showed that recombinant human IL-22 significantly enhanced human tubular epithelial cell proliferation and wound closure upon mechanical injury, and electric cell-substrate impedance sensing studies revealed that recombinant IL-22 sustained tubular epithelial barrier function upon injury. In contrast, IL-22 had no such direct effects on human fibroblasts. Together, in progressive kidney remodeling upon UUO, infiltrating immune cells secrete IL-22, which augments tubular epithelial integrity and epithelial barrier function, but does not affect vascular rarefaction or fibrogenesis. We conclude that IL-22 could represent a molecular target to specifically modulate tubular atrophy.
Item Type: | Journal article |
---|---|
Faculties: | Medicine |
Research Centers: | Center for Integrated Protein Science Munich (CIPSM) |
Subjects: | 500 Science > 540 Chemistry 600 Technology > 610 Medicine and health |
URN: | urn:nbn:de:bvb:19-epub-68165-7 |
ISSN: | 2051-817X |
Language: | English |
Item ID: | 68165 |
Date Deposited: | 19. Jul 2019, 12:24 |
Last Modified: | 04. Nov 2020, 13:50 |