Silencing myostatin increases area fraction of smooth muscle in the corpus cavernosum of pigs

Choe, Hak Myong; Gao, Kai; Paek, Hyo Jin; Liu, Xinyue; Li, Zhou-Yan; Quan, Biao-Hu; Yin, Xi-Jun

doi:10.1016/j.anireprosci.2022.107077

Cited by 3 publications

(7 citation statements)

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“…TAGLN is ubiquitously expressed in vascular and visceral smooth muscle as a marker of smooth muscle differentiation. In a model of myostatin homozygous mutant knockout pig, increased expression of TAGLN was noted in the penile corpus cavernosum, which could be a target for treating ED ( 50 ). Moreover, angiogenesis may be a possible link between TAGLN and depression ( 51 – 53 ).…”

Section: Discussionmentioning

confidence: 99%

Exploring potential genes and mechanisms linking erectile dysfunction and depression

Yuan,

Chen,

Sun

et al. 2023

Front. Endocrinol.

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BackgroundThe clinical correlation between erectile dysfunction (ED) and depression has been revealed in cumulative studies. However, the evidence of shared mechanisms between them was insufficient. This study aimed to explore common transcriptomic alterations associated with ED and depression.Materials and methodsThe gene sets associated with ED and depression were collected from the Gene Expression Omnibus (GEO) database. Comparative analysis was conducted to obtain common genes. Using R software and other appropriate tools, we conducted a range of analyses, including function enrichment, interactive network creation, gene cluster analysis, and transcriptional and post-transcriptional signature profiling. Candidate hub crosslinks between ED and depression were selected after external validation and molecular experiments. Furthermore, subpopulation location and disease association of hub genes were explored.ResultsA total of 85 common genes were identified between ED and depression. These genes strongly correlate with cell adhesion, redox homeostasis, reactive oxygen species metabolic process, and neuronal cell body. An interactive network consisting of 80 proteins and 216 interactions was thereby developed. Analysis of the proteomic signature of common genes highlighted eight major shared genes: CLDN5, COL7A1, LDHA, MAP2K2, RETSAT, SEMA3A, TAGLN, and TBC1D1. These genes were involved in blood vessel morphogenesis and muscle cell activity. A subsequent transcription factor (TF)–miRNA network showed 47 TFs and 88 miRNAs relevant to shared genes. Finally, CLDN5 and TBC1D1 were well-validated and identified as the hub crosslinks between ED and depression. These genes had specific subpopulation locations in the corpus cavernosum and brain tissue, respectively.ConclusionOur study is the first to investigate common transcriptomic alterations and the shared biological roles of ED and depression. The findings of this study provide insights into the referential molecular mechanisms underlying the co-existence between depression and ED.

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Section: Discussionmentioning

confidence: 99%

Exploring potential genes and mechanisms linking erectile dysfunction and depression

Yuan,

Chen,

Sun

et al. 2023

Front. Endocrinol.

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“…One of these MSTN -edited models, its progeny, or its crosses were further investigated . These include investigations on fiber-type distribution and expression of myosin heavy chain isoforms; shift from slow- to fast-twitch muscle fibers in skeletal muscle; internal organ size; semen quality and fertilization ability; reproductive trait characterization in MSTN -edited crosses; collagen-related pathological features (umbilical hernia and tippy toe standing); regulation of body fat deposition; fibrinogen levels and fibrin clot structure; esophageal striated muscle development and regulation of muscle fiber types; extraocular muscles; cardiac extracellular matrix; growth of smooth muscle in uterine horns of MSTN mutant gilts; smooth muscle content in corpus cavernosum of MSTN mutant boars; erythrocyte osmotic fragility, hematological parameters, and fatty acid composition of serum and erythrocyte membranes; miR-455-3p regulation of myoblast differentiation; composition and alteration of gut microbiota; analysis of meat and fatty acids characteristics; and development of a restriction enzyme-mediated PCR-RFLP assay for genotyping MSTN mutant pigs …”

Section: Targeting the Mstn Gene In Pigsmentioning

confidence: 99%

When Less Is More: Targeting the Myostatin Gene in Livestock for Augmenting Meat Production

Kalds

Zhou

Huang

et al. 2023

J. Agric. Food Chem.

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How to increase meat production is one of the main questions in animal breeding. Selection for improved body weight has been made and, due to recent genomic advances, naturally occurring variants that are responsible for controlling economically relevant phenotypes have been revealed. The myostatin (MSTN) gene, a superstar gene in animal breeding, was discovered as a negative controller of muscle mass. In some livestock species, natural mutations in the MSTN gene could generate the agriculturally desirable double-muscling phenotype. However, some other livestock species or breeds lack these desirable variants. Genetic modification, particularly gene editing, offers an unprecedented opportunity to induce or mimic naturally occurring mutations in livestock genomes. To date, various MSTN-edited livestock species have been generated using different gene modification tools. These MSTN gene-edited models have higher growth rates and increased muscle mass, suggesting the high potential of utilizing MSTN gene editing in animal breeding. Additionally, post-editing investigations in most livestock species support the favorable influence of targeting the MSTN gene on meat quantity and quality. In this Review, we provide a collective discussion on targeting the MSTN gene in livestock to further encourage its utilization opportunities. It is expected that, shortly, MSTN gene-edited livestock will be commercialized, and MSTN-edited meat will be on the tables of ordinary customers.

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“…In addition to skeletal muscles, MSTN also exists in smooth muscles [17,18]. To date, a large number of MSTN studies have focused on skeletal muscle [1,19,20], but only a few have focused on smooth muscle [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

“…The contraction of smooth muscle tissues is not voluntarily controlled; it is controlled by hormones and parasympathetic signals released through the autonomic nervous system and locally, such as calcium ions (Ca 2+ ) [24]. Studies have shown that MSTN has a regulatory effect on smooth muscles [21][22][23]. MSTN knockout can increase the smooth muscle area of the pig esophagus and penile corpus cavernosum and promote the proliferation of sow uterine smooth muscle cells [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

“…Studies have shown that MSTN has a regulatory effect on smooth muscles [21][22][23]. MSTN knockout can increase the smooth muscle area of the pig esophagus and penile corpus cavernosum and promote the proliferation of sow uterine smooth muscle cells [21][22][23]. However, the effect of MSTN knockout on bovine esophageal smooth muscle has not been reported.…”

Section: Introductionmentioning

confidence: 99%

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Combined Transcriptome and Metabolome Analysis of Smooth Muscle of Myostatin Knockout Cattle

Wang

et al. 2023

IJMS

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Myostatin (MSTN), a growth and differentiation factor, plays an important role in regulating skeletal muscle growth and development. MSTN knockout (MSTN-KO) leads to skeletal muscle hypertrophy and regulates metabolic homeostasis. Moreover, MSTN is also detected in smooth muscle. However, the effect of MSTN-KO on smooth muscle has not yet been reported. In this study, combined metabolome and transcriptome analyses were performed to investigate the metabolic and transcriptional profiling in esophageal smooth muscles of MSTN-KO Chinese Luxi Yellow cattle (n = 5, 24 months, average body weight 608.5 ± 17.62 kg) and wild-type (WT) Chinese Luxi Yellow cattle (n = 5, 24 months, average body weight 528.25 ± 11.03 kg). The transcriptome was sequenced using the Illumina Novaseq™ 6000 sequence platform. In total, 337 significantly up- and 129 significantly down-regulated genes were detected in the MSTN-KO cattle compared with the WT Chinese Luxi Yellow cattle. Functional enrichment analysis indicated that the DEGs were mainly enriched in 67 signaling pathways, including cell adhesion molecules, tight junction, and the cGMP-PKG signaling pathway. Metabolomics analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified 130 differential metabolites between the groups, with 56 up-regulated and 74 down-regulated in MSTN knockout cattle compared with WT cattle. Differential metabolites were significantly enriched in 31 pathways, including glycerophospholipid metabolism, histidine metabolism, glutathione metabolism, and purine metabolism. Transcriptome and metabolome were combined to analyze the significant enrichment pathways, and there were three metabolically related pathways, including histidine metabolism, purine metabolism, and arginine and proline metabolism. These results provide important references for in-depth research on the effect of MSTN knockout on smooth muscle.

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Silencing myostatin increases area fraction of smooth muscle in the corpus cavernosum of pigs

Cited by 3 publications

References 34 publications

Exploring potential genes and mechanisms linking erectile dysfunction and depression

Exploring potential genes and mechanisms linking erectile dysfunction and depression

When Less Is More: Targeting the Myostatin Gene in Livestock for Augmenting Meat Production

Combined Transcriptome and Metabolome Analysis of Smooth Muscle of Myostatin Knockout Cattle

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