Identification of key candidate genes and pathways revealing the protective effect of liraglutide on diabetic cardiac muscle by integrated bioinformatics analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32309328", "kind": "science-record", "revision": 9, "content_hash": "sha256:f2349782b49a846ce1f0c514643ca988746394e6eb05e8ff7f637f4446a6a74a", "created_at": "2026-11-01T15:40:59Z", "updated_at": "2026-11-01T22:44:46Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of key candidate genes and pathways revealing the protective effect of liraglutide on diabetic cardiac muscle by integrated bioinformatics analysis.", "doi": "10.21037/atm.2020.01.94", "pmid": "32309328", "authors": ["Ying Dong", "Shi Yan", "Guo-Yan Li", "Min-Nan Wang", "Lei Leng", "Qiang Li"], "journal": "Annals of translational medicine", "year": 2020, "abstract": "BACKGROUND: Diabetes mellitus is becoming a significant health problem with the International Diabetes Federation (IDF) expecting a startling 642 million diabetes patients by 2040. Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, is reported to protect against diabetic cardiomyopathy by binding to the receptor, GLP-1R. However, the underlying mechanism has yet to be clarified. This study aimed to investigate the underlying mechanisms and the effects of liraglutide on diabetic patient's cardiac muscles.\nMETHODS: GSE102194 genetic expression profiles were extracted from the Gene Expression Omnibus (GEO) database. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were carried out. Next, Cytoscape software was used to construct the protein-protein interaction (PPI) network of the differentially expressed genes (DEGs). DEGs were mapped onto a protein-protein interaction (PPI) network that comprised 249 nodes and 776 edges.\nRESULTS: A total of 520 DEGs were discovered, including 159 down-regulated genes and 361 up-regulated genes. DEGs that were upregulated were notably enriched in biological processes (BP) such as muscle system process, muscle system process, muscle structure development and anatomical structure morphogenesis while DEGs that were downregulated were rich in detection of chemical stimulus and neurological system process. KEGG pathway analysis showed the up-regulated DEGs were enriched in adrenergic signaling for cardiomyocytes, dopaminergic synapse, and circadian entrainment, while the down-regulated DEGs were enriched for factory transduction in 249 of the 520 tested samples. The modular analysis identified 4 modules that participated in some pathways associated with cardiac muscle contraction, hypertrophic cardiomyopathy (HCM), and MAPK signaling pathway.\nCONCLUSIONS: Our data showed that Glp-1 could decrease the protein expression of p38, JNK, ERK1/2, and MARS proteins induced by high glucose (22 mM, 72 h). This study highlights the potential physiological processes that take place in diabetic cardiac muscles exposed to liraglutide. Our findings elucidated the regulatory network in diabetic cardiomyopathy and might provide a novel diagnostic and therapeutic target for diabetic cardiomyopathy.", "claims": [{"id": "claim-data-access", "statement": "GSE102194 gene expression profiles were extracted from the GEO database. GSE102194, which was based on GPL17117 platform Affymetrix Rat Gene 2.0 ST Array) (10). The GSE102194 cohort comprised 6 samples, including the cardiac muscle of 3 liraglutide-treated rats and that of 3 controls.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32309328", "locator": "sections[3] \"Microarray data information\" paragraph 2", "quote": "GSE102194 gene expression profiles were extracted from the GEO database. GSE102194, which was based on GPL17117 platform Affymetrix Rat Gene 2.0 ST Array) (10). The GSE102194 cohort comprised 6 samples, including the cardiac muscle of 3 liraglutide-treated rats and that of 3 controls."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:32309328"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE102194"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE102194"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32309328", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/atm.2020.01.94", "sha256": "sha256:77d98e47d720883e775307b42030b6294127e2df29f57d0b3296bd70977f098e", "bytes": 35440, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.21037/atm.2020.01.94", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7154457", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE102194", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE102194", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE102194", "version": null, "note": "GSE102194 gene expression profiles were extracted from the GEO database. GSE102194, which was based on GPL17117 platform Affymetrix Rat Gene 2.0 ST Array) (10). The GSE102194 cohort comprised 6 samples, including the cardiac muscle of 3 liraglutide-treated rats and that of 3 controls.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "GSE102194 gene expression profiles were extracted from the GEO database. GSE102194, which was based on GPL17117 platform Affymetrix Rat Gene 2.0 ST Array) (10). The GSE102194 cohort comprised 6 samples, including the cardiac muscle of 3 liraglutide-treated rats and that of 3 controls.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM2730230", "GSM2730231", "GSM2730232", "GSM2730233", "GSM2730234", "GSM2730235"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "17117", "taxon": "Rattus norvegicus", "title": "Gene expression alternations in liraglutide treated rats cardiac muscle", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:32309328:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:0e6539591a353310ba0fca63507602adaa7fead9f3638ca5afc54f1c16663c6e", "bytes": 1723, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", 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significantly enriched KEGG pathway of differentially expressed genes", "structure": {"pmcid": "PMC7154457", "section_index": 16, "section_title": "GO term enrichment and KEGG pathway analyses", "row_count": 8, "column_count": 4}, "table": {"label": "Table 4", "caption": "The significantly enriched KEGG pathway of differentially expressed genes", "rows": [["Term", "Count", "P value", "FDR"], ["Up-regulated", "", ""], ["rno04261: adrenergic signaling in cardiomyocytes", "16", "2.20E-08", "2.76E-05"], ["rno04728: dopaminergic synapse", "15", "6.80E-08", "8.53E-05"], ["rno05031: amphetamine addiction", "9", "1.75E-05", "0.021963"], ["rno04540: gap junction", "10", "2.70E-05", "0.033829"], ["Down-regulated", "", ""], ["rno04740: olfactory transduction", "37", "7.92E-15", "7.78E-12"]], "row_count": 8, "column_count": 4, "numeric_cells": 20, "header_rows": 2, "locator": "section[16]/table-wrap[4]#t4"}}, {"id": "asset:table:pmid:32309328:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:cb302f5a4fd43ee245beef59fc98d3762179be69b99d15cf519af1dd7571ae49", "bytes": 1442, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[1]#t5", "version": null, "note": "The related KEGG pathways of different modules", "structure": {"pmcid": "PMC7154457", "section_index": 17, "section_title": "Identification of key candidate genes and pathways using protein-protein interaction network (PPI) and modular screening", "row_count": 23, "column_count": 3}, "table": {"label": "Table 5", "caption": "The related KEGG pathways of different modules", "rows": [["Term", "Count", "Genes"], ["Module 1", "", ""], ["rno04530: tight junction", "4", "MYH1, MYH4, ACTN2, ACTN3"], ["rno04670: leukocyte transendothelial migration", "3", "MYLPF, ACTN2, ACTN3"], ["rno04510: focal adhesion", "3", "MYLPF, ACTN2, ACTN3"], ["rno04810: regulation of actin cytoskeleton", "3", "MYLPF, ACTN2, ACTN3"], ["rno00010: glycolysis/gluconeogenesis", "2", "PGAM2, ENO3"], ["rno04520: adherens junction", "2", "ACTN2, ACTN3"], ["rno04260: cardiac muscle contraction", "2", "MYL3, TPM2"], ["rno05410: hypertrophic cardiomyopathy (HCM)", "2", "MYL3, TPM2"], ["rno01230: biosynthesis of amino acids", "2", "PGAM2, ENO3"], ["Module 2", "", ""], ["rno04540: gap junction", "6", "TUBB2B, TUBB2A, TUBB5, TUBA4A, TUBA1B, TUBB3"], ["rno04145: phagosome", "6", "TUBB2B, TUBB2A, TUBB5, TUBA4A, TUBA1B, TUBB3"], ["Module 3", "", ""], ["rno04010: MAPK signaling pathway", "2", "RPS6KA2, MRAS"], ["Module 4", "", ""], ["rno04721: synaptic vesicle cycle", "4", "SYT1, CPLX1, STXBP1, SNAP25"], ["rno04380: osteoclast differentiation", "4", "FOS, FYN, FOSB, JUNB"], ["rno05031: amphetamine addiction", "3", "PRKCA, FOS, FOSB"], ["rno04725: cholinergic synapse", "3", "PRKCA, FOS, FYN"], ["rno04010: MAPK signaling pathway", "3", "PRKCA, DUSP4, FOS"], ["rno04664: Fc epsilon RI 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