miR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis

Liu, Gang; Friggeri, Arnaud; Yang, Yanping; Milošević, Jadranka; Ding, Qiang; Thannickal, Victor J.; Kaminski, Naftali; Abraham, Edward

doi:10.1083/jcb1902oia3

Cited by 65 publications

(120 citation statements)

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“…These findings are fully consistent with recent data showing that miR-21 is upregulated in fibrosis of lung, heart, liver and kidney [6,12,23,32], while increased levels of miR-21 in fibroblasts have been found in several other conditions. Thus, Thum et al [43] showed that miR-21 was weakly expressed in normal myocardium, but after infarction miR-21 levels increased in cardiac fibroblasts, in direct correlation with increased atrial collagen content and reduced SPRY-1 expression.…”

Section: Mir-21 Upregulation and Its Implicationssupporting

confidence: 93%

“…Previous data also indicate that miR-21 inhibition can reduce fibrosis. Thus in a mouse cardiac hypertrophy model, miR-21 silencing inhibited interstitial fibrosis [43]; miR-21 antisense probes diminished the severity of induced lung fibrosis in mice and attenuated the pro-fibrogenic activity of TGF-β1 in fibroblasts [23]; and antagomiR-21 injection prevented fibrosis in a mouse model of heart infarction [1]. Our experiments on mdx mice showed that antagomiR-21 treatment effectively reduced not only levels of target transcripts but also extent of fibrosis and soluble collagen production.…”

Section: Mir-21 Downregulation As Anti-fibrotic Therapymentioning

confidence: 99%

“…MiR-21 was originally considered an oncomiR, as it is over-expressed in most cancer types [27], but recent data show that it is one of the most highly upregulated miRNAs during tissue injury, and that its persistent overexpression disrupts tissue repair and contributes to tissue fibrosis in heart [6], kidney [12], liver [32] and lung [23]. MiR-21 is also upregulated during the wound contraction and collagen deposition phases of skin wound healing [48], and promotes keratinocyte migration by inhibiting TIMP-3 [52].…”

Section: Introductionmentioning

confidence: 99%

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Opposing roles of miR-21 and miR-29 in the progression of fibrosis in Duchenne muscular dystrophy

Zanotti¹,

Gibertini²,

Curcio³

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Excessive extracellular matrix deposition progressively replacing muscle fibres is the endpoint of most severe muscle diseases. Recent data indicate major involvement of microRNAs in regulating pro- and anti-fibrotic genes. To investigate the roles of miR-21 and miR-29 in muscle fibrosis in Duchenne muscle dystrophy, we evaluated their expression in muscle biopsies from 14 patients, and in muscle-derived fibroblasts and myoblasts. In Duchenne muscle biopsies, miR-21 expression was significantly increased, and correlated directly with COL1A1 and COL6A1 transcript levels. MiR-21 expression was also significantly increased in Duchenne fibroblasts, more so after TGF-β1 treatment. In Duchenne fibroblasts the expression of miR-21 target transcripts PTEN (phosphatase and tensin homolog deleted on chromosome 10) and SPRY-1 (Sprouty homolog 1) was significantly reduced; while collagen I and VI transcript levels and soluble collagen production were significantly increased. MiR-29a and miR-29c were significantly reduced in Duchenne muscle and myoblasts, and miR-29 target transcripts, COL3A1, FBN1 and YY1, significantly increased. MiR-21 silencing in mdx mice reduced fibrosis in the diaphragm muscle and in both Duchenne fibroblasts and mdx mice restored PTEN and SPRY-1 expression, and significantly reduced collagen I and VI expression; while miR-29 mimicking in Duchenne myoblasts significantly decreased miR-29 target transcripts. These findings indicate that miR-21 and miR-29 play opposing roles in Duchenne muscle fibrosis and suggest that pharmacological modulation of their expression has therapeutic potential for reducing fibrosis in this condition.

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Section: Mir-21 Upregulation and Its Implicationssupporting

confidence: 93%

Section: Mir-21 Downregulation As Anti-fibrotic Therapymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Opposing roles of miR-21 and miR-29 in the progression of fibrosis in Duchenne muscular dystrophy

Zanotti¹,

Gibertini²,

Curcio³

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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show abstract

“…De maniè re inté ressante, de nombreuses é tudes ont é tabli son implication dans les phé nomè nes de carcinogenè se, d'inflammation, mais é galement dans le processus de fibrose, notamment aux niveaux pulmonaire [62], cardiaque [63] et ré nal [64].…”

Section: Mir-21unclassified

Implication des microARN dans la fibrose rénale

Hauwaert

Savary

Hennino

et al. 2015

Néphrologie & Thérapeutique

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“…Interestingly, WNT/b-catenin signalling downregulates let-7d expression [92]. miR-21 expression is increased in the lungs and serum from IPF patient [93,94] and can be induced by WNT/b-catenin signalling [95]. High levels of miR-21 can also be linked to enhanced WNT pathway activation as miR-21 targets and suppresses the expression of the WNT antagonist DKK2, thereby promoting WNT/b-catenin signalling [96].…”

Section: Wnt Signalling Pathwaymentioning

confidence: 99%