MicroRNA-24-3p promotes skeletal muscle differentiation and regeneration by regulating high mobility group AT-hook 1

Skeletal Muscle Differentiation

AbstractSkeletal muscle regenerates throughout the lifetime to maintain normal development, growth, and physiological function. Skeletal muscle regeneration occurs in a coordinated fashion and requires strict regulation of myogenic gene expression during the process. Numerous studies have established the critical role of microRNAs in regulating post-transcriptional gene expression in diverse biological processes including differentiation, development, and regeneration. We have revealed in an earlier study that a large number of microRNAs were differentially expressed during myoblast differentiation. Here, we report the role of one such microRNA, the miR-24-3p, in skeletal muscle differentiation and regeneration. miR-24-3p is induced during myoblast differentiation and skeletal muscle regeneration. Exogenous miR-24-3p promotes while inhibition of miR-24-3p represses myoblast differentiation. miR-24-3p promotes myoblast differentiation by directly targeting and regulating the high mobility group AT-hook 1 (HMGA1). Consistent with the finding that HMGA1 is a repressor of myogenic differentiation, the miR-24-3p-resistant form of HMGA1 devoid of 3’untranslated region, inhibits myoblast differentiation. Intramuscular injection of antagomirs specific to miR-24-3p into the tibialis anterior muscle prevents HMGA1 down-regulation and impairs regeneration. These findings provide evidence for the requirement of the miR-24-3p/HMGA1 axis for skeletal muscle differentiation and regeneration.

MicroRNA-24-3p promotes skeletal muscle differentiation and regeneration by regulating HMGA1

10.21203/rs.3.rs-976465/v1 ◽

2021 ◽

Author(s):

Paromita Dey ◽

Miles A Soyer ◽

Bijan K Dey

Keyword(s):

Skeletal Muscle ◽

Tibialis Anterior Muscle ◽

High Mobility ◽

Muscle Differentiation ◽

Muscle Stem Cells ◽

Downstream Target

Abstract Numerous studies have established the critical roles of microRNAs in regulating posttranscriptional gene expression in diverse biological processes. Here, we report on the role and mechanism of miR-24-3p in skeletal muscle differentiation and regeneration. miR-24-3p promotes myoblast differentiation and skeletal muscle regeneration by directly targeting high mobility group AT-hook 1 (HMGA1) and regulating it and its direct downstream target, the inhibitor of differentiation 3 (ID3). miR-24-3p knockdown in neonatal mice increases PAX7-positive proliferating muscle stem cells (MuSCs) by derepressing Hmga1 and Id3 . Similarly, inhibiting miR24-3p in the tibialis anterior muscle prevents Hmga1 and Id3 downregulation and impairs regeneration. These findings provide evidence that the miR-24-3p/HMGA1/ID3 axis is required for MuSC differentiation and regeneration in vivo .

Multiple Effects of High Mobility Group Box Protein 1 in Skeletal Muscle Regeneration

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.107.153429 ◽

2007 ◽

Vol 27 (11) ◽

pp. 2377-2383 ◽

Cited By ~ 63

Author(s):

Roberta De Mori ◽

Stefania Straino ◽

Anna Di Carlo ◽

Antonella Mangoni ◽

Giulio Pompilio ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Regeneration ◽

High Mobility ◽

High Mobility Group ◽

Skeletal Muscle Regeneration

Poly(ADP-ribose) Polymerase 1 (PARP1) restrains MyoD-dependent gene expression during muscle differentiation

Scientific Reports ◽

10.1038/s41598-020-72155-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Francesca Matteini ◽

Oriella Andresini ◽

Stefano Petrai ◽

Cecilia Battistelli ◽

Marianna Nicoletta Rossi ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Target Genes ◽

Muscle Differentiation ◽

Chromatin Accessibility ◽

Binding Regions ◽

Myogenic Factor ◽

Chromatin Proteins

Abstract The myogenic factor MyoD regulates skeletal muscle differentiation by interacting with a variety of chromatin-modifying complexes. Although MyoD can induce and maintain chromatin accessibility at its target genes, its binding and trans-activation ability can be limited by some types of not fully characterized epigenetic constraints. In this work we analysed the role of PARP1 in regulating MyoD-dependent gene expression. PARP1 is a chromatin-associated enzyme, playing a well recognized role in DNA repair and that is implicated in transcriptional regulation. PARP1 affects gene expression through multiple mechanisms, often involving the Poly(ADP-ribosyl)ation of chromatin proteins. In line with PARP1 down-regulation during differentiation, we observed that PARP1 depletion boosts the up-regulation of MyoD targets, such as p57, myogenin, Mef2C and p21, while its re-expression reverts this effect. We also found that PARP1 interacts with some MyoD-binding regions and that its presence, independently of the enzymatic activity, interferes with MyoD recruitment and gene induction. We finally suggest a relationship between the binding of PARP1 and the loss of the activating histone modification H3K4me3 at MyoD-binding regions. This work highlights not only a novel player in the epigenetic control of myogenesis, but also a repressive and catalytic-independent mechanisms by which PARP1 regulates transcription.

A MyoD-generated feed-forward circuit temporally patterns gene expression during skeletal muscle differentiation

Genes & Development ◽

10.1101/gad.1234304 ◽

2004 ◽

Vol 18 (19) ◽

pp. 2348-2353 ◽

Cited By ~ 123

Author(s):

B. H. Penn

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Muscle Differentiation ◽

Feed Forward

Kinin-B2 Receptor Activity in Skeletal Muscle Regeneration and Myoblast Differentiation

Stem Cell Reviews and Reports ◽

10.1007/s12015-018-9850-9 ◽

2018 ◽

Vol 15 (1) ◽

pp. 48-58 ◽

Cited By ~ 1

Author(s):

Janaina M. Alves ◽

Antonio H. Martins ◽

Claudiana Lameu ◽

Talita Glaser ◽

Nawal M. Boukli ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Regeneration ◽

Receptor Activity ◽

Myoblast Differentiation

The Role of Metabolic Remodeling in Macrophage Polarization and Its Effect on Skeletal Muscle Regeneration

Antioxidants and Redox Signaling ◽

10.1089/ars.2017.7420 ◽

2019 ◽

Vol 30 (12) ◽

pp. 1553-1598 ◽

Cited By ~ 10

Author(s):

Francesca De Santa ◽

Laura Vitiello ◽

Alessio Torcinaro ◽

Elisabetta Ferraro

Keyword(s):

Skeletal Muscle ◽

Muscle Regeneration ◽

Macrophage Polarization ◽

Metabolic Remodeling

The Potential Role of Insulin-Like Growth Factors in Skeletal Muscle Regeneration

Canadian Journal of Applied Physiology ◽

10.1139/h96-021 ◽

1996 ◽

Vol 21 (4) ◽

pp. 236-250 ◽

Cited By ~ 19

Author(s):

Jamie MacGregor ◽

Wade S. Parkhouse

Keyword(s):

Skeletal Muscle ◽

Growth Hormone ◽

Growth Factors ◽

Muscle Regeneration ◽

Potential Role ◽

Tissue Growth ◽

Tissue Type ◽

Insulin Like Growth Factors

The role of the insulin-like growth factors I and II (IGF-I and IGF-II), previously known as the somatomedins, in general growth and development of various tissues has been known for many years. Thought of exclusively as endocrine factors produced by the liver, and under the control of growth hormone, the somatomedins were known as the intermediaries by which growth hormone exerted its cellular effects during tissue growth and maturation. Eventually it was discovered that virtually every tissue type is capable of autocrine production of the IGFs, and their involvement in skeletal muscle tissue repair and regeneration became apparent. Recent advances in technology have allowed the characterisation of many of the different growth factors believed to play a role in muscle regeneration, and experimental manipulations of cells in culture have provided insight into the effects of the various growth factors on the myoblast. This paper explores the potential role of the IGFs in skeletal muscle regeneration. A critical role of IGF-II in terminal differentiation of proliferating muscle precurser cells following injury is proposed. Key words: growth factors, myogenesis, skeletal muscle regeneration

Myocyte-derived Tnfsf14 is a survival factor necessary for myoblast differentiation and skeletal muscle regeneration

Cell Death and Disease ◽

10.1038/cddis.2015.375 ◽

2015 ◽

Vol 6 (12) ◽

pp. e2026-e2026 ◽

Cited By ~ 9

Author(s):

R J Waldemer-Streyer ◽

J Chen

Keyword(s):

Skeletal Muscle ◽

Muscle Regeneration ◽

Survival Factor

Zfp422 promotes skeletal muscle differentiation by regulating EphA7 to induce appropriate myoblast apoptosis

Cell Death and Differentiation ◽

10.1038/s41418-019-0448-9 ◽

2019 ◽

Vol 27 (5) ◽

pp. 1644-1659 ◽

Cited By ~ 1

Author(s):

Yaping Nie ◽

Shufang Cai ◽

Renqiang Yuan ◽

Suying Ding ◽

Xumeng Zhang ◽

...

Keyword(s):

Skeletal Muscle ◽

Zinc Finger ◽

Muscle Development ◽

Zinc Finger Protein ◽

Critical Role ◽

Muscle Differentiation ◽

C2c12 Cells ◽

Finger Protein

Abstract Zinc finger protein 422 (Zfp422) is a widely expressed zinc finger protein that serves as a transcriptional factor to regulate downstream gene expression, but until now, little is known about its roles in myogenesis. We found here that Zfp422 plays a critical role in skeletal muscle development and regeneration. It highly expresses in mouse skeletal muscle during embryonic development. Specific knockout of Zfp422 in skeletal muscle impaired embryonic muscle formation. Satellite cell-specific Zfp422 deletion severely inhibited muscle regeneration. Myoblast differentiation and myotube formation were suppressed in Zfp422-deleted C2C12 cells, isolated primary myoblasts, and satellite cells. Chromatin Immunoprecipitation Sequencing (ChIP-Seq) revealed that Zfp422 regulated ephrin type-A receptor 7 (EphA7) expression by binding an upstream 169-bp DNA sequence, which was proved to be an enhancer of EphA7. Knocking EphA7 down in C2C12 cells or deleting Zfp422 in myoblasts will inhibit cell apoptosis which is required for myoblast differentiation. These results indicate that Zfp422 is essential for skeletal muscle differentiation and fusion, through regulating EphA7 expression to maintain proper apoptosis.