Role of miR-145 in cardiac myofibroblast differentiation

Wang, Yaosheng; Li, Shuhong; Guo, Jian; Mihic, Anton; Wu, Jun; Sun, Lu; Davis, K.A.; Weisel, Richard D.; Li, Ren‐Ke

doi:10.1016/j.yjmcc.2013.08.007

Cited by 79 publications

(62 citation statements)

References 16 publications

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“…Furthermore, we identified several miRNA-target gene pairs with a potential role in skin scarring that needed experimental confirmation (Table 1). In addition, we analyzed miR-101 (14) and miR-133b (15), which were reported to play a role in fibrosis of tissues other than the skin, and miR-145, which was shown to be deregulated in lung and heart fibrosis as well as keloid fibroblasts (16,17,24).…”

Section: Discussionmentioning

confidence: 99%

“…Previously, miR-145 was shown to play a role in fibroblast-to-myofibroblast differentiation in lung and heart tissue (16,17). However, it is known that fibroblasts from internal organs have dramatic differences in gene expression patterns compared with dermal fibroblasts (25,26).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, we chose to analyze miR-101 (14), miR-133b (15) and miR-145 (16,17), which were reported to play a role in fibrosis of tissues other than skin, but might have a similar role in skin fibrosis and scarring.…”

Section: Identification Of Candidate Mirnas Potentially Involved In Hmentioning

confidence: 99%

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miR-145 Contributes to Hypertrophic Scarring of the Skin by Inducing Myofibroblast Activity

Gras

Ratuszny

Hadamitzky

et al. 2015

Mol Med

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Hyperthrophic scarring of the skin is caused by excessive activity of skin myofibroblasts after wound healing and often leads to functional and/or aesthetic disturbance with significant impairment of patient quality of life. MicroRNA (miRNA) gene therapies have recently been proposed for complex processes such as fibrosis and scarring. In this study, we focused on the role of miR-145 in skin scarring and its influence in myofibroblast function. Our data showed not only a threefold increase of miR-145 levels in skin hypertrophic scar tissue but also in transforming growth factor β1 (TGF-β1)-induced skin myofibroblasts compared with healthy skin or nontreated fibroblasts (p < 0.001). Consistent with the upregulation of miR-145 induced by TGF-β1 stimulation of fibroblasts, the expression of Kruppel-like factor 4 (KLF4) was decreased by 50% and α-smooth muscle actin (α-SMA) protein expression showed a threefold increase. Both could be reversed by miR-145 inhibition (p < 0.05). Restoration of KLF4 levels equally abrogated TGF-β1-induced α-SMA expression. These data demonstrate that TGF-β1 induces miR-145 expression in fibroblasts, which in turn inhibits KLF4, a known inhibitor of α-SMA, hence upregulating α-SMA expression. Furthermore, treatment of myofibroblasts with a miR-145 inhibitor strongly decreased their α-1 type I collagen expression, TGF-β1 secretion, contractile force generation and migration. These data demonstrate that upregulation of miR-145 plays an important role in the differentiation and function of skin myofibroblasts. Additionally, inhibition of miR-145 significantly reduces skin myofibroblast activity. Taken together, these results suggest that miR-145 is a promising therapeutic target to prevent or reduce hypertrophic scarring of the skin.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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miR-145 Contributes to Hypertrophic Scarring of the Skin by Inducing Myofibroblast Activity

Gras

Ratuszny

Hadamitzky

et al. 2015

Mol Med

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“…1 To whom correspondence may be addressed. involved in the different diseases, such as cardiac myofibroblast differentiation, pulmonary arterial hypertension, and microvasculature (21)(22)(23). In addition, miR-145 is also associated with different kinds of human cancers, in which miR-145 regulates PAK4 in human colon cells and is down-regulated in human ovarian cancer and so on (24 -26).…”

mentioning

confidence: 99%

MicroRNA-145 Modulates N6-Methyladenosine Levels by Targeting the 3′-Untranslated mRNA Region of the N6-Methyladenosine Binding YTH Domain Family 2 Protein

Yang

Feng

et al. 2017

Journal of Biological Chemistry

221

212

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“…9 Under certain pathophysiological conditions, however, this cell type preference seems to be partly abandoned, leading to enhanced expression of miR-143/145 in activated ECs 7 and fibroblasts. 10,11 The joint suppression of specific target mRNAs by miR-143/145 contributes to a contractile phenotype, 10 an interpretation that is supported by mice with genetic deficiency of miR-143/145, which also display reduced vascular tone and blood pressure control. 9 A question that evolved from these previous findings was whether miR-143/145, which is expressed at high levels in VSMCs, may also represent a signal to neighboring cells.…”

Section: Article See P 1753mentioning

confidence: 99%