Differentially Expressed mRNA in Streptozotocin-Induced Diabetic Bladder Using RNA Sequencing Analysis
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Purpose: To detect elements governing the pathogenesis of diabetic cystopathy (DC), mRNA sequencing was carried out for bladder tissues from normal rats and those with induced diabetes mellitus (DM). This research therefore offers possible underlying molecular pathways for the advancement of DC in relation to differential mRNA expression, together with visceral functional and architectural alterations noted in individuals with this condition. Methods: An intraperitoneal injection of streptozotocin (STZ) was utilized to provoke DM in male Sprague-Dawley rats. Dysregulation and significant variations between normal rats and those with induced DM were then identified by a fold change of ≥1.5 with a false discovery rate P<0.05. Hierarchical clustering/heat map and Gene Ontology/DAVID reference sources were generated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein-protein interaction analysis were then performed. Results: The diabetic rodent group exhibited a greater residual urine volume (4.0±0.4 mL) than their control counterparts (0.7±0.2 mL, P<0.01) at 12 weeks after diagnosis of diabetes. Expression analysis revealed 16 upregulated and 4 downregulated genes in STZDM bladder samples. A notable increase in expression was seen in PTHLH, TNFAIP6, PRC1, MAPK10, LOC686120, CASQ2, ACTG2, PDLIM3, FCHSD1, DBN1, NKD2, PDLIM7, ATF4, RBPMS2, ITGB1 and HSPB8. A notable decrease in expression was seen in SREBLF1, PBGFR1, PBLD1 and CELF1. Major genetic themes associated with mRNA upregulation and downregulation ware identified via Gene Ontology analysis and KEGG pathways. Protein to protein interaction analysis detected PDLIM3, PDLIM7, ITGB1, ACTG2 as core high frequency nodes within the network. Conclusions: Changes in mRNA expression together with biological process and pathways that contribute to the etiologies underlying visceral impairment of the bladder in DM are evident. Our strategy is promising for recognizing mRNAs exclusive to the bladder in DM that might offer useful targets for diagnosis and treatment.
Abstract
Purpose: To detect elements governing the pathogenesis of diabetic cystopathy (DC), mRNA sequencing was carried out for bladder tissues from normal rats and those with induced diabetes mellitus (DM). This research therefore offers possible underlying molecular pathways for the advancement of DC in relation to differential mRNA expression, together with visceral functional and architectural alterations noted in individuals with this condition. Methods: An intraperitoneal injection of streptozotocin (STZ) was utilized to provoke DM in male Sprague-Dawley rats. Dysregulation and significant variations between normal rats and those with induced DM were then identified by a fold change of ≥1.5 with a false discovery rate P<0.05. Hierarchical clustering/heat map and Gene Ontology/DAVID reference sources were generated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein-protein interaction analysis were then performed. Results: The diabetic rodent group exhibited a greater residual urine volume (4.0±0.4 mL) than their control counterparts (0.7±0.2 mL, P<0.01) at 12 weeks after diagnosis of diabetes. Expression analysis revealed 16 upregulated and 4 downregulated genes in STZDM bladder samples. A notable increase in expression was seen in PTHLH, TNFAIP6, PRC1, MAPK10, LOC686120, CASQ2, ACTG2, PDLIM3, FCHSD1, DBN1, NKD2, PDLIM7, ATF4, RBPMS2, ITGB1 and HSPB8. A notable decrease in expression was seen in SREBLF1, PBGFR1, PBLD1 and CELF1. Major genetic themes associated with mRNA upregulation and downregulation ware identified via Gene Ontology analysis and KEGG pathways. Protein to protein interaction analysis detected PDLIM3, PDLIM7, ITGB1, ACTG2 as core high frequency nodes within the network. Conclusions: Changes in mRNA expression together with biological process and pathways that contribute to the etiologies underlying visceral impairment of the bladder in DM are evident. Our strategy is promising for recognizing mRNAs exclusive to the bladder in DM that might offer useful targets for diagnosis and treatment.
참고문헌 (32)
- Bonow RO, "The diabetes epidemic : a national and global crisis", Am J Med, 116(Suppl 5A), pp.2S~10S (2004)
- Engelgau MM, "Addressing the burden of diabetes in the 21st century : better care and primary prevention", J Am Soc Nephrol, 14(7 Suppl 2), pp.S88~S91 (2003)
- Permutt MA, "Genetic epidemiology of diabetes", J Clin Invest, 115, pp.1431~1439 (2005)
- Wild S, "Global prevalence of diabetes : estimates for the year 2000 and projections for 2030", Diabetes Care, 27, pp.1047~1053 (2004)
- Zimmet P, "Global and societal implications of the diabetes epidemic", Nature, 414, pp.782~787 (2001)
- Alloussi S, "Micturition disorder as a sequela of sacral autonomic diabetic neuropathy", Urologe A, 24, pp.291~295 (1985)
- Brown JS, "Urologic complications of diabetes", Diabetes Care, 28, pp.177~185 (2005)
- Faerman I, "Asymptomatic neurogenic bladder in juvenile diabetics", Diabetologia, 7, pp.168~172 (1971)
- Frimodt-Møller C, "Treatment of diabetic cystopathy", Ann Intern Med, 92, pp.327~328 (1980)
- Kaplan SA, "Urodynamic findings in patients with diabetic cystopathy", J Urol, 153, pp.342~344 (1995)
- Menéndez V, "Urodynamic evaluation in simultaneous insulin-dependent diabetes mellitus and end stage renal disease", J Urol, 155, pp.2001~2004 (1996)
- Levin RM, "Update on bladder smooth-muscle physiology", World J Urol, 12, pp.226~232 (1994)
- Nakahara T, "MaxiK channel-triggered negative feedback system is preserved in the urinary bladder smooth muscle from streptozotocin-induced diabetic rats", J Smooth Muscle Res, 40, pp.97~109 (2004)
- Christ GJ, "Effects of streptozotocin-induced diabetes on bladder and erectile(dys)function in the same rat in vivo", BJU Int, 97, pp.1076~1082 (2006)
- Daneshgari F, "Time dependent changes in diabetic cystopathy in rats include compensated and decompensated bladder function", J Urol, 176, pp.380~386 (2006)
- Liu G, "Temporal diabetes-and diuresis-induced remodeling of the urinary bladder in the rat", Am J Physiol Regul Integr Comp Physiol, 291, pp.R837~R843 (2006)
- Langmead B, "Fast gapped-read alignment with Bowtie 2", Nat Methods, 9, pp.357~359 (2012)
- Quinlan AR, "BEDTools : a flexible suite of utilities for comparing genomic features", Bioinformatics, 26, pp.841~842 (2010)
- Gentleman RC, "Bioconductor : open software development for computational biology and bioinformatics", Genome Biol, 5, pp.R80~ (2004)
- Henderson JR, "ALP and MLP distribution during myofibrillogenesis in cultured cardiomyocytes", Cell Motil Cytoskeleton, 54, pp.254~265 (2003)
- Ueyama H, "A HindIII DNA polymorphism in the human enteric type smooth muscle actin gene(ACTSG)", Nucleic Acids Res, 19, pp.411~ (1991)
- Reszka AA, "Identification of amino acid sequences in the integrin beta 1 cytoplasmic domain implicated in cytoskeletal association", J Cell Biol, 117, pp.1321~1330 (1992)
- Hua X, "Structure of the human gene encoding sterol regulatory element binding protein-1(SREBF1) and localization of SREBF1 and SREBF2 to chromosomes 17p11.2 and 22q13", Genomics, 25, pp.667~673 (1995)
- Shim AH, "Structures of a platelet-derived growth factor", propeptide complex and a plateletderived growth factor, Proc Natl Acad Sci U S A, pp.2010, 107[DOI]
- Timchenko LT, "Identification of a(CUG)n triplet repeat RNA-binding protein and its expression in myotonic dystrophy", Nucleic Acids Res, 24, pp.4407~4414 (1996)
- Pittenger G, "Nerve growth factor and diabetic neuropathy", Exp Diabesity Res, 4, pp.271~285 (2003)
- Yasuda H, "Diabetic neuropathy and nerve regeneration", Prog Neurobiol, 69, pp.229~285 (2003)
- Yuan Z, "Diabetic cystopathy : a review", J Diabetes, 7, pp.442~447 (2015)
- Daneshgari F, "Diabetic bladder dysfunction : current translational knowledge", J Urol, 182(6 Suppl), pp.S18~S26 (2009)
- Szklarczyk D, "The STRING database in 2017 : quality-controlled protein-protein association networks, made broadly accessible", Nucleic Acids Res, 45(D1), pp.D362~D368 (2017)
- Shannon P, "Cytoscape : a software environment for integrated models of biomolecular interaction networks", Genome Res, 13, pp.2498~2504 (2003)
- Cline MS, "Integration of biological networks and gene expression data using Cytoscape", Nat Protoc, 2, pp.2366~2382 (2007)
