Investigation of single nucleotide polymorphisms in differentially expressed genes and proteins reveals the genetic basis of skeletal muscle growth differences between Tibetan and Large White pigs

Article

Author: Xiong, Heli ; Zhang, Yan ; Zhao, Zhiyong

Objective: Skeletal muscle growth is an important economic trait for meat production, with notable differences between Tibetan pigs (TIBPs, a slow-growing breed) and Large White pigs (LWPs, a fast-growing breed). However, the genetic underpinnings of this disparity remain unclear.Methods: In the current study, we integrated differentially expressed genes (DEGs) and proteins (DEPs) from 60-day-old embryonic muscle tissue, along with whole-genome single nucleotide polymorphisms (SNPs) displaying absolute allele frequency differences (ΔAF) of 0.5 or more between the TIBP and LWP breeds, to unravel the genetic factors influencing skeletal muscle growth.Results: Our analysis revealed 3,499 DEGs and 628 DEPs with SNPs having a ΔAF equal to or greater than 0.5. Further functional analysis identified 145 DEGs and 23 DEPs involved in biological processes related to skeletal muscle development, and 22 DEGs and 3 DEPs implicated in the mechanistic target of rapamycin kinase signaling pathway, which is known for positively regulating protein synthesis. Among these genes, several DEGs and DEPs, enriched with TIPB-specific SNPs in regulatory or/and coding regions, showed marked ΔAF between the TIBP and LWP breeds, including MYF5, MYOF, ASB2, PDE9A, SDC1, PDGFRA, MYOM2, ACVR1, ZIC3, COL11A1, TGFBR1, EDNRA, TGFB2, PDE4D, PGAM2, GRK2, SCN4B, CACNA1S, MYL4, IGF1, and FOXO1. Additionally, genes such as CAPN3, MYOM2, and PGAM2, identified as both DEPs and DEGs related to skeletal muscle development, contained multiple TIBP-specific and LWP-predominant SNPs in regulatory and/or coding regions, underscoring significant ΔAF differences between the two breeds.Conclusion: This comprehensive investigation of SNPs in DEGs and DEPs identified a significant number of SNPs and genes related to skeletal muscle development during the prenatal stage. These findings not only shed light on potential causal genes for muscle divergence between the TIBP and LWP breeds but also offer valuable insights for pig breeding strategies aimed at enhancing meat production.

17 Feb 2018·Clinical and Experimental HypertensionQ4 · MEDICINE

Gene expression and gene associations during the development of heart failure with preserved ejection fraction in the Dahl salt sensitive model of hypertension

Q4 · MEDICINE

Review

Author: Rabkin, Simon W. ; Cho, Hyokeun ; Yim, Jeffrey

Gene expression and associations were examined in a model of heart failure with preserved ejection fraction (HFpEF), a condition with minimal effective treatment. Genes with at least two studies showing significant changes in Dahl rat with heart failure were examined by meta-analysis. Significantly increased in expression were iNOS, p47phox, ADM, ANP, OPN, ACE, MCP-1, GP91PHOX, ICAM-1, TGF-β1, CTGF, ET-1, p22phox, ETB, BNP, ETA, MMP13, Col1a1, MMP2, TIMP1, Col3a1, Il-1β, β-MHC, ECE1, MMP14, AGT, and MMP9. In contrast, GLUT4, VEGF, eNOS, HIF-1α, and PGC1-α were significantly decreased in expression. The top biological process clusters identified in Database for Annotation, Visualization and Integrated Discovery, ToppGene, and PANTHER were collagen metabolic process, cellular ion homeostasis, regulation of cell migration, and response to decreased oxygen levels. These data suggest refocusing understanding of the pathophysiology of HFpEF to pathways involved in collagen metabolism, cell migration likely for inflammatory cells, and responses to decreased oxygen levels. Abbreviations Inducible nitric oxide synthase (INOS), neutrophil cytosolic factor 1 (p47phox), adrenomedullin (ADM), atrial natriuretic peptide (ANP), osteopontin (OPN/SPP1), angiotensin converting enzyme (ACE), monocyte chemotactic protein 1 (MCP-1), cytochrome b-245 beta polypeptide (gp91phox), intercellular adhesion molecule 1 (ICAM-1), transforming growth factor beta 1 (TGF-β1), connective tissue growth factor (CTGF), endothelin-1 (ET-1), cytochrome B-245, alpha polypeptide (p22phox), endothelin receptor type B (ETB/EDNRB), brain natriuretic peptide (BNP), endothelin receptor type A (ETA/EDNRA), matrix metallopeptidase 13 (MMP13), type I collagen (Col1a1), matrix metallopeptidase 2 (MMP2), TIMP metallopeptidase inhibitor 1 (TIMP1), Type III collagen (Col3a1), interleukin 1 beta (IL-1β), beta myocin heavy chain (β-MHC), endothelin converting enzyme 1 (ECE1) matrix metallopeptidase 14 (MMP14), angiotensinogen (AGT), angiotensin II receptor Type 1 (AT1R), cytochrome C oxidase I (COX1), fms-like tyrosine kinase 1 (FLT1), TIMP metallopeptidase inhibitor 2 (TIMP2), phospholamban (PLN), vascular cell adhesion molecule 1 (VCAM1), extracellular matrix (ECM).

01 Aug 2017·Immunologic ResearchQ4 · MEDICINE

Pathogenesis of systemic sclerosis—current concept and emerging treatments

Q4 · MEDICINE

Review

Author: Mitoma, Hiroki ; Nakahara, Takeshi ; Tsuji, Gaku ; Mitoma, Chikage ; Uchi, Hiroshi ; Furue, Masutaka ; Chiba, Takahito ; Kadono, Takafumi

Systemic sclerosis (SSc) is an intractable multifaceted disease with high mortality. Although its pathogenesis is not fully understood, recent studies have advanced our knowledge on SSc. The cardinal pathological features of SSc are autoimmunity, vasculopathy, and fibrosis. The B cells in SSc are constitutively activated and lead to the production of a plethora of autoantibodies, such as anti-topoisomerase I and anti-centromere antibodies. In addition to these autoantibodies, which are valuable for diagnostic criteria or biomarkers, many other autoantibodies targeting endothelial cells, including endothelin type A receptor and angiotensin II type I receptor, are known to be functional and induce activation or apoptosis of endothelial cells. The autoantibody-mediated endothelial cell perturbation facilitates inflammatory cell infiltration, cytokine production, and myofibroblastic transformation of fibroblasts and endothelial cells. Profibrotic cytokines, such as transforming growth factor β, connective tissue growth factor, interleukin 4/interleukin 13, and interleukin 6, play a pivotal role in collagen production from myofibroblasts. Specific treatments targeting these causative molecules may improve the clinical outcomes of patients with SSc. In this review, we summarize recent topics on the pathogenesis (autoantibodies, vasculopathy, and fibrosis), animal models, and emerging treatments for SSc.

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