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Meis1 is specifically upregulated in kidney myofibroblasts during aging and injury but is not required for kidney homeostasis or fibrotic response.

ABSTRACT: The homeobox transcription factor Meis1 is required for mammalian development, and its overexpression plays a role in tumorigenesis, especially leukemia. Meis1 is known to be expressed in kidney stroma, but its function in kidney is undefined. We hypothesized that Meis1 may regulate stromal cell proliferation in kidney development and disease and tested the hypothesis using cell lineage tracing and cell-specific Meis1 deletion in development, aging, and fibrotic disease. We observed strong expression of Meis1 in platelet-derived growth factor receptor-?-positive pericytes and perivascular fibroblasts, both in adult mouse kidney and to a lesser degree in human kidney. Either bilateral ischemia-reperfusion injury or aging itself led to strong upregulation of Meis1 protein and mRNA in kidney myofibroblasts, and genetic lineage analysis confirmed that Meis1-positive cells proliferate as they differentiate into myofibroblasts after injury. Conditional deletion of Meis1 in all kidney stroma with two separate tamoxifen-inducible Cre recombinase drivers had no phenotype with the exception of consistent induction of the tubular injury marker kidney injury molecule-1 (Kim-1) only in Meis1 mutants. Further examination of Kim-1 expression revealed linkage disequilibrium of Kim-1 and Meis1, such that Meis1 mutants carried the longer BALB/c Kim-1 allele. Unexpectedly, we report that this Kim-1 allele is expressed at baseline in wild-type BALB/c mice, without any associated abnormalities, including long-term fibrosis, as predicted from the literature. We conclude that Meis1 is specifically expressed in stroma and myofibroblasts of mouse and human kidney, that it is not required for kidney development, disease, or aging, and that BALB/c mice unexpectedly express Kim-1 protein at baseline without other kidney abnormality.

SUBMITTER: Chang-Panesso M

PROVIDER: S-EPMC6139520 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Meis1 is specifically upregulated in kidney myofibroblasts during aging and injury but is not required for kidney homeostasis or fibrotic response.

Chang-Panesso Monica M Kadyrov Farid F FF Machado Flavia G FG Kumar Ashish A Humphreys Benjamin D BD

American journal of physiology. Renal physiology 20180328 2

The homeobox transcription factor Meis1 is required for mammalian development, and its overexpression plays a role in tumorigenesis, especially leukemia. Meis1 is known to be expressed in kidney stroma, but its function in kidney is undefined. We hypothesized that Meis1 may regulate stromal cell proliferation in kidney development and disease and tested the hypothesis using cell lineage tracing and cell-specific Meis1 deletion in development, aging, and fibrotic disease. We observed strong expre ...[more]

PMID: 29592525

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Dataset Information

Meis1 is specifically upregulated in kidney myofibroblasts during aging and injury but is not required for kidney homeostasis or fibrotic response.

Publications

Meis1 is specifically upregulated in kidney myofibroblasts during aging and injury but is not required for kidney homeostasis or fibrotic response.

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