Dataset Information

Reduction of type IV collagen by upregulated miR-29 in normal elderly mouse and klotho-deficient, senescence-model mouse.

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.

SUBMITTER: Takahashi M

PROVIDER: S-EPMC3490916 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Reduction of type IV collagen by upregulated miR-29 in normal elderly mouse and klotho-deficient, senescence-model mouse.

Takahashi Masaki M Eda Akiko A Fukushima Tatsunobu T Hohjoh Hirohiko H

PloS one 20121106 11

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, wer ...[more]

PMID: 23139829

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Project description:BackgroundIn chronic liver disease, hepatic stellate cells (HSC) transdifferentiate into myofibroblasts, promoting extracellular matrix (ECM) synthesis and deposition. Stimulation of HSC by transforming growth factor-? (TGF-?) is a crucial event in liver fibrogenesis due to its impact on myofibroblastic transition and ECM induction. In contrast, hepatocyte growth factor (HGF), exerts antifibrotic activities. Recently, miR-29 has been reported to be involved in ECM synthesis. We therefore studied the influence of HGF and TGF-? on the miR-29 collagen axis in HSC.MethodologyHSC, isolated from rats, were characterized for HGF and Met receptor expression by Real-Time PCR and Western blotting during culture induced myofibroblastic transition. Then, the levels of TGF-?, HGF, collagen-I and -IV mRNA, in addition to miR-29a and miR-29b were determined after HGF and TGF-? stimulation of HSC or after experimental fibrosis induced by bile-duct obstruction in rats. The interaction of miR-29 with 3'-untranslated mRNA regions (UTR) was analyzed by reporter assays. The repressive effect of miR-29 on collagen synthesis was studied in HSC treated with miR-29-mimicks by Real-Time PCR and immunoblotting.Principal findingsThe 3'-UTR of the collagen-1 and -4 subtypes were identified to bind miR-29. Hence, miR-29a/b overexpression in HSC resulted in a marked reduction of collagen-I and -IV synthesis. Conversely, a decrease in miR-29 levels is observed during collagen accumulation upon experimental fibrosis, in vivo, and after TGF-? stimulation of HSC, in vitro. Finally, we show that during myofibroblastic transition and TGF-? exposure the HGF-receptor, Met, is upregulated in HSC. Thus, whereas TGF-? stimulation leads to a reduction in miR-29 expression and de-repression of collagen synthesis, stimulation with HGF was definitely associated with highly elevated miR-29 levels and markedly repressed collagen-I and -IV synthesis.ConclusionsUpregulation of miRNA-29 by HGF and downregulation by TGF-? take part in the anti- or profibrogenic response of HSC, respectively.

Dataset Information

Reduction of type IV collagen by upregulated miR-29 in normal elderly mouse and klotho-deficient, senescence-model mouse.

Publications

Reduction of type IV collagen by upregulated miR-29 in normal elderly mouse and klotho-deficient, senescence-model mouse.

Similar Datasets

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