High mobility group box 2 regulates skeletal muscle development through ribosomal protein S6 kinase 1

Fāng, Yīng; Feng, Liang; Yuan, Renqiang; Zhu, Qi; Cai, Shaohui; Chen, Keren; Zhang, Junyan; Luo, Xiaorong; Chen, Yaosheng; Mo, Delin

doi:10.1096/fj.202001183r

Cited by 6 publications

(4 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…14,44 Maintaining HMGB2 expression is required for the proliferation of mouse hepatocyte cells 12 and is critical for satellite cell proliferation and muscle regeneration. 45 These results suggest that HMGB2 is essential for cell proliferation. The pathogenesis of PH involves an imbalance between cell proliferation and death, which occurs with inflammation and shares several features analogous to carcinogenesis 20 ; therefore, investigating the role of HMGB2 in PH is of significant interest.…”

Section: Discussionmentioning

confidence: 91%

HMGB2 Release Promotes Pulmonary Hypertension and Predicts Severity and Mortality of Patients With Pulmonary Arterial Hypertension

Kong,

Liu,

et al. 2024

ATVB

View full text Add to dashboard Cite

BACKGROUND: Pulmonary hypertension (PH) is a progressive and life-threatening disease characterized by pulmonary vascular remodeling, which involves aberrant proliferation and apoptosis resistance of the pulmonary arterial smooth muscle cells (PASMCs), resembling the hallmark characteristics of cancer. In cancer, the HMGB2 (high-mobility group box 2) protein promotes the pro-proliferative/antiapoptotic phenotype. However, the function of HMGB2 in PH remains uninvestigated. METHODS: Smooth muscle cell (SMC)–specific HMGB2 knockout or HMGB2-OE (HMGB2 overexpression) mice and HMGB2 silenced rats were used to establish hypoxia+Su5416 (HySu)-induced PH mouse and monocrotaline-induced PH rat models, respectively. The effects of HMGB2 and its underlying mechanisms were subsequently elucidated using RNA-sequencing and cellular and molecular biology analyses. Serum HMGB2 levels were measured in the controls and patients with pulmonary arterial (PA) hypertension. RESULTS: HMGB2 expression was markedly increased in the PAs of patients with PA hypertension and PH rodent models and was predominantly localized in PASMCs. SMC-specific HMGB2 deficiency or silencing attenuated PH development and pulmonary vascular remodeling in hypoxia+Su5416-induced mice and monocrotaline-treated rats. SMC-specific HMGB2 overexpression aggravated hypoxia+Su5416-induced PH. HMGB2 knockdown inhibited PASMC proliferation in vitro in response to PDGF-BB (platelet-derived growth factor-BB). In contrast, HMGB2 protein stimulation caused the hyperproliferation of PASMCs. In addition, HMGB2 promoted PASMC proliferation and the development of PH by RAGE (receptor for advanced glycation end products)/FAK (focal adhesion kinase)-mediated Hippo/YAP (yes-associated protein) signaling suppression. Serum HMGB2 levels were significantly increased in patients with PA hypertension, and they correlated with disease severity, predicting worse survival. CONCLUSIONS: Our findings indicate that targeting HMGB2 might be a novel therapeutic strategy for treating PH. Serum HMGB2 levels could serve as a novel biomarker for diagnosing PA hypertension and determining its prognosis.

show abstract

Section: Discussionmentioning

confidence: 91%

HMGB2 Release Promotes Pulmonary Hypertension and Predicts Severity and Mortality of Patients With Pulmonary Arterial Hypertension

Kong,

Liu,

et al. 2024

ATVB

View full text Add to dashboard Cite

show abstract

“…Furthermore, increased DCN expression in pectoral muscle during the late embryonic stage is associated with muscle weakness in low-score-normal (LSN) individuals [ 31 , 32 ]. Posttranslational modifications mediated by 90 kDa ribosomal protein S6 kinase (RPS6KA1) are necessary for muscle differentiation and hypertrophy [ 33 , 34 ]. S6K deficiency may lead to reduced protein synthesis and specifically trigger muscle cell atrophy in skeletal muscle cells [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Integrating miRNA and full-length transcriptome profiling to elucidate the mechanism of muscle growth in Muscovy ducks reveals key roles for miR-301a-3p/ANKRD1

Huang,

Xiong,

Zhang

et al. 2024

BMC Genomics

View full text Add to dashboard Cite

Background The popularity of Muscovy ducks is attributed not only to their conformation traits but also to their slightly higher content of breast and leg meat, as well as their stronger-tasting meat compared to that of typical domestic ducks. However, there is a lack of comprehensive systematic research on the development of breast muscle in Muscovy ducks. In addition, since the number of skeletal muscle myofibers is established during the embryonic period, this study conducted a full-length transcriptome sequencing and microRNA sequencing of the breast muscle. Muscovy ducks at four developmental stages, namely Embryonic Day 21 (E21), Embryonic Day 27 (E27), Hatching Day (D0), and Post-hatching Day 7 (D7), were used to isolate total RNA for analysis. Results A total of 68,161 genes and 472 mature microRNAs were identified. In order to uncover deeper insights into the regulation of mRNA by miRNAs, we conducted an integration of the differentially expressed miRNAs (known as DEMs) with the differentially expressed genes (referred to as DEGs) across various developmental stages. This integration allowed us to make predictions regarding the interactions between miRNAs and mRNA. Through this analysis, we identified a total of 274 DEGs that may serve as potential targets for the 68 DEMs. In the predicted miRNA‒mRNA interaction networks, let-7b, miR-133a-3p, miR-301a-3p, and miR-338-3p were the hub miRNAs. In addition, multiple DEMs also showed predicted target relationships with the DEGs associated with skeletal system development. These identified DEGs and DEMs as well as their predicted interaction networks involved in the regulation of energy homeostasis and muscle development were most likely to play critical roles in facilitating the embryo-to-hatchling transition. A candidate miRNA, miR-301a-3p, exhibited increased expression during the differentiation of satellite cells and was downregulated in the breast muscle tissues of Muscovy ducks at E21 compared to E27. A dual-luciferase reporter assay suggested that the ANKRD1 gene, which encodes a transcription factor, is a direct target of miR-301a-3p. Conclusions miR-301a-3p suppressed the posttranscriptional activity of ANKRD1, which is an activator of satellite cell proliferation, as determined with gain- and loss-of-function experiments. miR-301a-3p functions as an inducer of myogenesis by targeting the ANKRD1 gene in Muscovy ducks. These results provide novel insights into the early developmental process of black Muscovy breast muscles and will improve understanding of the underlying molecular mechanisms.

show abstract

“…The maintenance of HMGB2 expression at a basal level is essential for satellite cell proliferation and muscle regeneration [191]. It has been shown that HMGB2 interacts with ribosomal protein kinase S6 beta-1 (S6K1) and regulates its activity during cell proliferation.…”

Section: Decreased Hmgb2 Expressionmentioning

confidence: 99%

Structure and Functions of HMGB2 Protein

Starkova

Polyanichko

Tomilin

et al. 2023

IJMS

View full text Add to dashboard Cite

High-Mobility Group (HMG) chromosomal proteins are the most numerous nuclear non-histone proteins. HMGB domain proteins are the most abundant and well-studied HMG proteins. They are involved in variety of biological processes. HMGB1 and HMGB2 were the first members of HMGB-family to be discovered and are found in all studied eukaryotes. Despite the high degree of homology, HMGB1 and HMGB2 proteins differ from each other both in structure and functions. In contrast to HMGB2, there is a large pool of works devoted to the HMGB1 protein whose structure–function properties have been described in detail in our previous review in 2020. In this review, we attempted to bring together diverse data about the structure and functions of the HMGB2 protein. The review also describes post-translational modifications of the HMGB2 protein and its role in the development of a number of diseases. Particular attention is paid to its interaction with various targets, including DNA and protein partners. The influence of the level of HMGB2 expression on various processes associated with cell differentiation and aging and its ability to mediate the differentiation of embryonic and adult stem cells are also discussed.

show abstract

High mobility group box 2 regulates skeletal muscle development through ribosomal protein S6 kinase 1

Cited by 6 publications

References 36 publications

HMGB2 Release Promotes Pulmonary Hypertension and Predicts Severity and Mortality of Patients With Pulmonary Arterial Hypertension

HMGB2 Release Promotes Pulmonary Hypertension and Predicts Severity and Mortality of Patients With Pulmonary Arterial Hypertension

Integrating miRNA and full-length transcriptome profiling to elucidate the mechanism of muscle growth in Muscovy ducks reveals key roles for miR-301a-3p/ANKRD1

Structure and Functions of HMGB2 Protein

Contact Info

Product

Resources

About