Abstract
MicroRNA (miRNA), a small non-coding RNA that functions as a mediator in gene silencing, plays important roles in gene regulation in various vital functions and activities. Here we show that the miR-29 members are upregulated in klotho-deficient [klotho(-/-)] mice, a senescence-model animal, and also in normal elderly ICR mice relative to wild-type littermates and young ICR mice. In addition, levels of type IV collagen, a major component of basement membranes and a putative target of miR-29, were lower in klotho(-/-) and elderly ICR mice than in wild-type littermates and young ICR mice. RNA degradation mediated by miR-29 may participate in the suppression of type IV collagen, both in vivo and in vitro. Taken together, our current findings suggest that the miR-29 upregulated in aging may be involved in the downregulation of type IV collagen, leading to a possible weakening of the basal membrane in senescent tissues, and miR-29 may be a useful molecular marker of senescence.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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8-Hydroxy-2'-Deoxyguanosine
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Aging / genetics*
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Animals
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Collagen Type IV / metabolism*
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Creatinine / blood
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Deoxyguanosine / analogs & derivatives
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Deoxyguanosine / blood
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Gene Expression Profiling
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Gene Knockdown Techniques
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Gene Silencing
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Genes, Reporter
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Glucuronidase / deficiency*
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Glucuronidase / metabolism
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HEK293 Cells
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Humans
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Klotho Proteins
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Lysine / blood
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Male
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Mice
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Mice, Inbred ICR
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MicroRNAs / genetics*
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MicroRNAs / metabolism
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Models, Biological*
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Up-Regulation / genetics*
Substances
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Collagen Type IV
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MIRN29 microRNA, mouse
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MicroRNAs
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8-Hydroxy-2'-Deoxyguanosine
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Creatinine
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Glucuronidase
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Klotho Proteins
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Deoxyguanosine
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Lysine
Grants and funding
This work was supported by research grants from the Ministry of Health, Labour and Welfare of Japan and by Grants-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.