1 4336 111 MICRORNAS: THE UNDERLYING MEDIATORS OF PATHOGENETIC PROCESSES IN VASCULAR COMPLICATIONS OF DIABETES. DIABETES MELLITUS CAUSES CHRONIC COMPLICATIONS PRIMARILY AFFECTING THE VASCULATURE OF VARIOUS ORGANS, RISKING PATIENTS FOR RENAL FAILURE, VISION LOSS AND HEART FAILURE. A NEWLY DISCOVERED CLASS OF MOLECULES, MICRORNAS, MAY BE IMPORTANT IN THE GENESIS OF THESE PATHOLOGIC PROCESSES. MICRORNAS REGULATE GENE EXPRESSION AT THE POST-TRANSCRIPTIONAL LEVEL BY INHIBITING TARGET MESSENGER RNA TRANSLATION. IN DISEASE STATES, HOWEVER, THE EXPRESSION OF MICRORNAS OFTEN IS ALTERED, RESULTING IN FURTHER ALTERED EXPRESSION (MOSTLY OVEREXPRESSION) OF DOWNSTREAM TARGET GENES. INTERESTINGLY, RESTORING MICRORNA EXPRESSION TO NORMAL LEVELS CAN CORRECT DOWNSTREAM EFFECTS AND PREVENT DIABETES-ASSOCIATED CHANGES. INVESTIGATIONS INTO MICRORNA INVOLVED IN VARIOUS PATHOGENETIC PROCESSES MEDIATING DIABETIC NEPHROPATHY, RETINOPATHY AND CARDIOMYOPATHY ARE HIGHLIGHTED IN THIS REVIEW. FUTURE DIRECTIONS OF MICRORNA IN THERAPEUTICS AND DIAGNOSTICS ARE ALSO DISCUSSED. IT IS OUR INTENT TO HELP THE READER APPRECIATE THE DIVERSE INTERACTIONS MICRORNAS HAVE IN CELLULAR SIGNALLING AND HOW UNDERSTANDING EPIGENETIC ELEMENTS, SUCH AS MICRORNAS, POTENTIALLY CAN YIELD NEW THERAPEUTIC STRATEGIES. 2013 2 6377 39 THE ROLE OF NON-CODING RNAS IN DIABETIC NEPHROPATHY: POTENTIAL APPLICATIONS AS BIOMARKERS FOR DISEASE DEVELOPMENT AND PROGRESSION. DIABETIC NEPHROPATHY, A PROGRESSIVE KIDNEY DISEASE THAT DEVELOPS SECONDARY TO DIABETES, IS THE MAJOR CAUSE OF CHRONIC KIDNEY DISEASE IN DEVELOPED COUNTRIES, AND CONTRIBUTES SIGNIFICANTLY TO INCREASED MORBIDITY AND MORTALITY AMONG INDIVIDUALS WITH DIABETES. ALTHOUGH THE CAUSES OF DIABETIC NEPHROPATHY ARE NOT FULLY UNDERSTOOD, RECENT STUDIES DEMONSTRATE A ROLE FOR EPIGENETIC FACTORS IN THE DEVELOPMENT OF THE DISEASE. FOR EXAMPLE, NON-CODING RNA (NCRNA) MOLECULES, INCLUDING MICRORNAS (MIRNAS), HAVE BEEN SHOWN TO BE FUNCTIONALLY IMPORTANT IN MODULATING RENAL RESPONSE TO HYPERGLYCEMIA AND PROGRESSION OF DIABETIC NEPHROPATHY. CHARACTERIZATION OF MIRNA EXPRESSION IN DIABETIC NEPHROPATHY FROM STUDIES OF ANIMAL MODELS OF DIABETES, AND IN VITRO INVESTIGATIONS USING DIFFERENT TYPES OF KIDNEY CELLS ALSO SUPPORT THIS ROLE. THE GOAL OF THIS REVIEW, THEREFORE, IS TO SUMMARIZE THE CURRENT STATE OF KNOWLEDGE OF SPECIFIC NCRNAS INVOLVED IN THE DEVELOPMENT OF DIABETIC NEPHROPATHY, WITH A FOCUS ON THE POTENTIAL ROLE OF MIRNAS TO SERVE AS SENSITIVE, NON-INVASIVE BIOMARKERS OF KIDNEY DISEASE AND PROGRESSION. NON-CODING RNAS ARE CURRENTLY RECOGNIZED AS POTENTIALLY IMPORTANT REGULATORS OF GENES INVOLVED IN PROCESSES RELATED TO THE DEVELOPMENT OF DIABETIC NEPHROPATHY, AND AS SUCH, REPRESENT VIABLE TARGETS FOR BOTH CLINICAL DIAGNOSTIC STRATEGIES AND THERAPEUTIC INTERVENTION. 2013 3 607 32 BEYOND GENETICS: EPIGENETIC CODE IN CHRONIC KIDNEY DISEASE. EPIGENETICS REFERS TO A HERITABLE CHANGE IN THE PATTERN OF GENE EXPRESSION THAT IS MEDIATED BY A MECHANISM SPECIFICALLY NOT DUE TO ALTERATIONS IN THE PRIMARY NUCLEOTIDE SEQUENCE. WELL-KNOWN EPIGENETIC MECHANISMS ENCOMPASS DNA METHYLATION, CHROMATIN REMODELING (HISTONE MODIFICATIONS), AND RNA INTERFERENCE. FUNCTIONALLY, EPIGENETICS PROVIDES AN EXTRA LAYER OF TRANSCRIPTIONAL CONTROL AND PLAYS A CRUCIAL ROLE IN NORMAL PHYSIOLOGICAL DEVELOPMENT, AS WELL AS IN PATHOLOGICAL CONDITIONS. ABERRANT DNA METHYLATION IS IMPLICATED IN IMMUNE DYSFUNCTION, INFLAMMATION, AND INSULIN RESISTANCE. EPIGENETIC CHANGES MAY BE RESPONSIBLE FOR 'METABOLIC MEMORY' AND DEVELOPMENT OF MICRO- AND MACROVASCULAR COMPLICATIONS OF DIABETES. MICRORNAS ARE CRITICAL IN THE MAINTENANCE OF GLOMERULAR HOMEOSTASIS AND HENCE RNA INTERFERENCE MAY BE IMPORTANT IN THE PROGRESSION OF RENAL DISEASE. RECENT STUDIES HAVE SHOWN THAT EPIGENETIC MODIFICATIONS ORCHESTRATE THE EPITHELIAL-MESENCHYMAL TRANSITION AND EVENTUALLY FIBROSIS OF THE RENAL TISSUE. OXIDATIVE STRESS, INFLAMMATION, HYPERHOMOCYSTEINEMIA, AND UREMIC TOXINS COULD INDUCE EPIMUTATIONS IN CHRONIC KIDNEY DISEASE. EPIGENETIC ALTERATIONS ARE ASSOCIATED WITH INFLAMMATION AND CARDIOVASCULAR DISEASE IN PATIENTS WITH CHRONIC KIDNEY DISEASE. REVERSIBLE NATURE OF THE EPIGENETIC CHANGES GIVES A UNIQUE OPPORTUNITY TO HALT OR EVEN REVERSE THE DISEASE PROCESS THROUGH TARGETED THERAPEUTIC STRATEGIES. 2011 4 4451 27 MOLECULAR MECHANISMS AND FUNCTIONS OF LNCRNAS IN THE INFLAMMATORY REACTION OF DIABETES MELLITUS. DIABETES IS A CHRONIC INFLAMMATORY STATE, AND SEVERAL STUDIES HAVE SHOWN THAT THE MECHANISMS OF INSULIN RESISTANCE AND ABNORMAL ISLET BETA-CELL FUNCTION IN DIABETES ARE CLOSELY RELATED TO INFLAMMATORY REACTIONS. INFLAMMATION PLAYS A CRITICAL ROLE IN DIABETIC COMPLICATIONS. LONG NONCODING RNAS (LNCRNAS), A NEW AREA OF GENOMIC RESEARCH FOR GENE REGULATION, HAVE COMPLEX BIOLOGICAL FUNCTIONS IN VARIOUS ASPECTS OF CELLULAR BIOLOGICAL ACTIVITY. RECENT STUDIES HAVE SHOWN THAT LNCRNAS ARE ASSOCIATED WITH THE REGULATION OF INFLAMMATORY RESPONSES IN VARIOUS WAYS, INCLUDING AT THE EPIGENETIC, TRANSCRIPTIONAL, AND POSTTRANSCRIPTIONAL LEVELS. THIS PAPER PRESENTS A BRIEF REVIEW OF STUDIES ON THE MECHANISMS OF LNCRNAS IN DIABETIC INFLAMMATION. THE PURPOSE OF THIS ARTICLE IS TO DETERMINE THE ROLE OF LNCRNAS IN THE PROCESS OF DIABETIC INFLAMMATION AND TO PROVIDE NEW STRATEGIES FOR THE USE OF LNCRNAS IN THE TREATMENTS FOR DIABETIC INFLAMMATION. 2021 5 3640 32 INCREASED EXTRACELLULAR MATRIX PROTEIN PRODUCTION IN CHRONIC DIABETIC COMPLICATIONS: IMPLICATIONS OF NON-CODING RNAS. MANAGEMENT OF CHRONIC DIABETIC COMPLICATIONS REMAINS A MAJOR MEDICAL CHALLENGE WORLDWIDE. ONE OF THE CHARACTERISTIC FEATURES OF ALL CHRONIC DIABETIC COMPLICATIONS IS AUGMENTED PRODUCTION OF EXTRACELLULAR MATRIX (ECM) PROTEINS. SUCH ECM PROTEINS ARE DEPOSITED IN ALL TISSUES AFFECTED BY CHRONIC COMPLICATIONS, ULTIMATELY CAUSING ORGAN DAMAGE AND DYSFUNCTION. A CONTRIBUTING FACTOR TO THIS PATHOGENETIC PROCESS IS GLUCOSE-INDUCED ENDOTHELIAL DAMAGE, WHICH INVOLVES PHENOTYPIC TRANSFORMATION OF ENDOTHELIAL CELLS (ECS). THIS PHENOTYPIC TRANSITION OF ECS, FROM A QUIESCENT STATE TO AN ACTIVATED DYSFUNCTIONAL STATE, CAN BE MEDIATED THROUGH ALTERATIONS IN THE SYNTHESIS OF CELLULAR PROTEINS. IN THIS REVIEW, WE DISCUSSED THE ROLES OF NON-CODING RNAS, SPECIFICALLY MICRORNAS (MIRNAS) AND LONG NON-CODING RNAS (LNCRNAS), IN SUCH PROCESSES. WE FURTHER OUTLINED OTHER EPIGENETIC MECHANISMS REGULATING THE BIOGENESIS AND/OR FUNCTION OF NON-CODING RNAS. OVERALL, WE BELIEVE THAT BETTER UNDERSTANDING OF SUCH MOLECULAR PROCESSES MAY LEAD TO THE DEVELOPMENT OF NOVEL BIOMARKERS AND THERAPEUTIC STRATEGIES IN THE FUTURE. 2019 6 2195 36 EPIGENETIC MODIFICATION MECHANISMS INVOLVED IN INFLAMMATION AND FIBROSIS IN RENAL PATHOLOGY. THE GROWING INCIDENCE OF OBESITY, HYPERTENSION, AND DIABETES, COUPLED WITH THE AGING OF THE POPULATION, IS INCREASING THE PREVALENCE OF RENAL DISEASES IN OUR SOCIETY. CHRONIC KIDNEY DISEASE (CKD) IS CHARACTERIZED BY PERSISTENT INFLAMMATION, FIBROSIS, AND LOSS OF RENAL FUNCTION LEADING TO END-STAGE RENAL DISEASE. NOWADAYS, CKD TREATMENT HAS LIMITED EFFECTIVENESS UNDERSCORING THE IMPORTANCE OF THE DEVELOPMENT OF INNOVATIVE THERAPEUTIC OPTIONS. RECENT STUDIES HAVE IDENTIFIED HOW EPIGENETIC MODIFICATIONS PARTICIPATE IN THE SUSCEPTIBILITY TO CKD AND HAVE EXPLAINED HOW THE ENVIRONMENT INTERACTS WITH THE RENAL CELL EPIGENOME TO CONTRIBUTE TO RENAL DAMAGE. EPIGENETIC MECHANISMS REGULATE CRITICAL PROCESSES INVOLVED IN GENE REGULATION AND DOWNSTREAM CELLULAR RESPONSES. THE MOST RELEVANT EPIGENETIC MODIFICATIONS THAT PLAY A CRITICAL ROLE IN RENAL DAMAGE INCLUDE DNA METHYLATION, HISTONE MODIFICATIONS, AND CHANGES IN MIRNA LEVELS. IMPORTANTLY, THESE EPIGENETIC MODIFICATIONS ARE REVERSIBLE AND, THEREFORE, A SOURCE OF POTENTIAL THERAPEUTIC TARGETS. HERE, WE WILL EXPLAIN HOW EPIGENETIC MECHANISMS MAY REGULATE ESSENTIAL PROCESSES INVOLVED IN RENAL PATHOLOGY AND HIGHLIGHT SOME POSSIBLE EPIGENETIC THERAPEUTIC STRATEGIES FOR CKD TREATMENT. 2018 7 4668 31 NEW INSIGHTS INTO MOLECULAR MECHANISMS OF EPIGENETIC REGULATION IN KIDNEY DISEASE. THE NUMBER OF PATIENTS WITH KIDNEY FAILURE HAS INCREASED IN RECENT YEARS. DIFFERENT FACTORS CONTRIBUTE TO THE PROGRESSION OF CHRONIC KIDNEY DISEASE, INCLUDING GLOMERULAR SCLEROSIS, ATHEROSCLEROSIS OF THE RENAL ARTERIES AND TUBULOINTERSTITIAL FIBROSIS. TUBULOINTERSTITIAL INJURY IS INDUCED BY HYPOXIA AND OTHER INFLAMMATORY SIGNALS, LEADING TO FIBROBLAST ACTIVATION. TECHNOLOGICAL ADVANCES USING HIGH-THROUGHPUT SEQUENCING HAS ENABLED THE DETERMINATION OF THE EXPRESSION PROFILE OF ALMOST ALL GENES, REVEALING THAT GENE EXPRESSION IS INTRICATELY REGULATED BY DNA METHYLATION, HISTONE MODIFICATION, CHANGES IN CHROMOSOME CONFORMATION, LONG NON-CODING RNAS AND MICRORNAS. THESE EPIGENETIC MODIFICATIONS ARE STORED AS CELLULAR EPIGENETIC MEMORY. EPIGENETIC MEMORY LEADS TO ADULT-ONSET DISEASE OR AGEING IN THE LONG TERM AND MAY POSSIBLY PLAY AN IMPORTANT ROLE IN THE KIDNEY DISEASE PROCESS. HEREIN WE EMPHASIZE THE IMPORTANCE OF CLARIFYING THE MOLECULAR MECHANISMS UNDERLYING EPIGENETIC MODIFICATIONS BECAUSE THIS MAY LEAD TO THE DEVELOPMENT OF NEW THERAPEUTIC TARGETS IN KIDNEY DISEASE. 2016 8 4289 31 MICRORNA IN OSTEOARTHRITIS. OSTEOARTHRITIS (OA) IS THE MOST PREVALENT DEGENERATIVE JOINT DISEASE AND IS ACCOMPANIED BY PAIN AND JOINT DYSFUNCTION. ITS CLINICAL TREATMENT TENDS TO BE UNSATISFACTORY. NOVEL TARGETS IN OA INCLUDE GENES THAT ARE INVOLVED IN OA PATHOPHYSIOLOGY AND HAVE BEEN DISCOVERED USING GENE NETWORK, EPIGENETIC AND MICRORNA (MIRNA) APPROACHES. MIRNA HAS BEEN IMPLICATED IN IMPORTANT CELLULAR PROCESSES SUCH AS LIPID METABOLISM, APOPTOSIS, DIFFERENTIATION AND ORGAN DEVELOPMENT. THE IMPORTANCE OF MIRNA REGULATION IN CELLULAR FUNCTION IS BECOMING INCREASINGLY CLEAR AS NEW MIRNA TARGETS ARE REVEALED. THE PRESENT REVIEW SUMMARIZES THE CURRENT EVIDENCE OF THE IMPORTANT ROLE PLAYED BY MIRNA IN DETERMINING THE COMPLEX GENE EXPRESSION PATTERNS OF OA CHONDROCYTES AND THEIR ROLE IN THE REGULATION OF TRANSCRIPTION, AND POSSIBLE DEMETHYLATION MECHANISMS THAT MIGHT BE APPLICABLE IN OA. IN SUMMARY, MIRNA MAY HAVE IMPORTANT DIAGNOSTIC AND THERAPEUTIC POTENTIAL, AND MIGHT PROVIDE A NOVEL MEANS OF TREATING OA. 2011 9 2163 36 EPIGENETIC MECHANISMS IN DIABETIC VASCULAR COMPLICATIONS. THERE HAS BEEN A RAPID INCREASE IN THE INCIDENCE OF DIABETES AS WELL THE ASSOCIATED VASCULAR COMPLICATIONS. BOTH GENETIC AND ENVIRONMENTAL FACTORS HAVE BEEN IMPLICATED IN THESE PATHOLOGIES. INCREASING EVIDENCE SUGGESTS THAT EPIGENETIC FACTORS PLAY A KEY ROLE IN THE COMPLEX INTERPLAY BETWEEN GENES AND THE ENVIRONMENT. ACTIONS OF MAJOR PATHOLOGICAL MEDIATORS OF DIABETES AND ITS COMPLICATIONS SUCH AS HYPERGLYCAEMIA, OXIDANT STRESS, AND INFLAMMATORY FACTORS CAN LEAD TO DYSREGULATED EPIGENETIC MECHANISMS THAT AFFECT CHROMATIN STRUCTURE AND GENE EXPRESSION. FURTHERMORE, PERSISTENCE OF THIS ALTERED STATE OF THE EPIGENOME MAY BE THE UNDERLYING MECHANISM CONTRIBUTING TO A 'METABOLIC MEMORY' THAT RESULTS IN CHRONIC INFLAMMATION AND VASCULAR DYSFUNCTION IN DIABETES EVEN AFTER ACHIEVING GLYCAEMIC CONTROL. FURTHER EXAMINATION OF EPIGENETIC MECHANISMS BY ALSO TAKING ADVANTAGE OF RECENTLY DEVELOPED NEXT-GENERATION SEQUENCING TECHNOLOGIES CAN PROVIDE NOVEL INSIGHTS INTO THE PATHOLOGY OF DIABETES AND ITS COMPLICATIONS AND LEAD TO THE DISCOVERY OF MUCH NEEDED NEW DRUG TARGETS FOR THESE DISEASES. IN THIS REVIEW, WE HIGHLIGHT THE ROLE OF EPIGENETICS IN DIABETES AND ITS VASCULAR COMPLICATIONS, AND RECENT TECHNOLOGICAL ADVANCES THAT HAVE SIGNIFICANTLY ACCELERATED THE FIELD. 2011 10 1505 33 DNA METHYLATION AND HISTONE MODIFICATION IN HYPERTENSION. SYSTEMIC HYPERTENSION, WHICH EVENTUALLY RESULTS IN HEART FAILURE, RENAL FAILURE OR STROKE, IS A COMMON CHRONIC HUMAN DISORDER THAT PARTICULARLY AFFECTS ELDERS. ALTHOUGH MANY SIGNALING PATHWAYS INVOLVED IN THE DEVELOPMENT OF HYPERTENSION HAVE BEEN REPORTED OVER THE PAST DECADES, WHICH HAS LED TO THE IMPLEMENTATION OF A WIDE VARIETY OF ANTI-HYPERTENSIVE THERAPIES, ONE HALF OF ALL HYPERTENSIVE PATIENTS STILL DO NOT HAVE THEIR BLOOD PRESSURE CONTROLLED. THE FRONTIER IN UNDERSTANDING THE MOLECULAR MECHANISMS UNDERLYING HYPERTENSION HAS NOW ADVANCED TO THE LEVEL OF EPIGENOMICS. PARTICULARLY, INCREASING EVIDENCE IS EMERGING THAT DNA METHYLATION AND HISTONE MODIFICATIONS PLAY AN IMPORTANT ROLE IN GENE REGULATION AND ARE INVOLVED IN ALTERATION OF THE PHENOTYPE AND FUNCTION OF VASCULAR CELLS IN RESPONSE TO ENVIRONMENTAL STRESSES. THIS REVIEW SEEKS TO HIGHLIGHT THE RECENT ADVANCES IN OUR KNOWLEDGE OF THE EPIGENETIC REGULATIONS AND MECHANISMS OF HYPERTENSION, FOCUSING ON THE ROLE OF DNA METHYLATION AND HISTONE MODIFICATION IN THE VASCULAR WALL. A BETTER UNDERSTANDING OF THE EPIGENOMIC REGULATION IN THE HYPERTENSIVE VESSEL MAY LEAD TO THE IDENTIFICATION OF NOVEL TARGET MOLECULES THAT, IN TURN, MAY LEAD TO NOVEL DRUG DISCOVERIES FOR THE TREATMENT OF HYPERTENSION. 2018 11 2532 32 EPIGENETICS IN ATHEROSCLEROSIS AND INFLAMMATION. ATHEROSCLEROSIS IS A MULTIFACTORIAL DISEASE WITH A SEVERE BURDEN ON WESTERN SOCIETY. RECENT INSIGHTS INTO THE PATHOGENESIS OF ATHEROSCLEROSIS UNDERSCORE THE IMPORTANCE OF CHRONIC INFLAMMATION IN BOTH THE INITIATION AND PROGRESSION OF VASCULAR REMODELLING. EXPRESSION OF IMMUNOREGULATORY MOLECULES BY VASCULAR WALL COMPONENTS WITHIN THE ATHEROSCLEROTIC LESIONS IS ACCORDINGLY THOUGHT TO CONTRIBUTE TO THE ONGOING INFLAMMATORY PROCESS. BESIDES GENE REGULATORY PROTEINS (TRANSCRIPTION FACTORS), EPIGENETIC MECHANISMS ALSO PLAY AN ESSENTIAL AND FUNDAMENTAL ROLE IN THE TRANSCRIPTIONAL CONTROL OF GENE EXPRESSION. THESE EPIGENETIC MECHANISMS CHANGE THE ACCESSIBILITY OF CHROMATIN BY DNA METHYLATION AND HISTONE MODIFICATIONS. EPIGENETIC MODULATORS ARE THUS CRITICALLY INVOLVED IN THE REGULATION OF VASCULAR, IMMUNE AND TISSUE-SPECIFIC GENE EXPRESSION WITHIN THE ATHEROSCLEROTIC LESION. IMPORTANTLY, EPIGENETIC PROCESSES ARE REVERSIBLE AND MAY PROVIDE AN EXCELLENT THERAPEUTIC TARGET. THE CONCEPT OF EPIGENETIC REGULATION IS GRADUALLY BEING RECOGNIZED AS AN IMPORTANT FACTOR IN THE PATHOGENESIS OF ATHEROSCLEROSIS. RECENT RESEARCH PROVIDES AN ESSENTIAL LINK BETWEEN INFLAMMATION AND REPROGRAMMING OF THE EPIGENOME. IN THIS REVIEW WE THEREFORE DISCUSS THE BASIS OF EPIGENETIC REGULATION - AND THE CONTRIBUTION THEREOF IN THE REGULATION OF INFLAMMATORY PROCESSES IN GENERAL AND DURING ATHEROSCLEROSIS IN PARTICULAR. MOREOVER WE HIGHLIGHT POTENTIAL THERAPEUTIC INTERVENTIONS BASED ON EPIGENETIC MECHANISMS. 2010 12 3826 33 INVESTIGATION OF EPIGENETICS IN KIDNEY CELL BIOLOGY. EPIGENETICS IS THE STUDY OF HERITABLE CHANGES IN DNA OR ITS ASSOCIATED PROTEINS EXCEPT MUTATIONS IN GENE SEQUENCE. EPIGENETIC REGULATION PLAYS FUNDAMENTAL ROLES IN THE PROCESSES OF KIDNEY CELL BIOLOGY THROUGH THE ACTION OF DNA METHYLATION, CHROMATIN MODIFICATIONS VIA EPIGENETIC REGULATORS AND INTERACTION VIA TRANSCRIPTION FACTORS, AND NONCODING RNA SPECIES. KIDNEY DISEASES, INCLUDING ACUTE KIDNEY INJURY, CHRONIC KIDNEY DISEASE, NEPHRITIC AND NEPHROTIC SYNDROMES, PYELONEPHRITIS AND POLYCYSTIC KIDNEY DISEASES ARE DRIVEN BY ABERRANT ACTIVITY IN NUMEROUS SIGNALING PATHWAYS IN EVEN INDIVIDUAL KIDNEY CELL. EPIGENETIC ALTERATIONS, INCLUDING DNA METHYLATION, HISTONE ACETYLATION AND METHYLATION, NONCODING RNAS, AND PROTEIN POSTTRANSLATIONAL MODIFICATIONS, COULD DISRUPT ESSENTIAL PATHWAYS THAT PROTECT THE RENAL CELLS FROM UNCONTROLLED GROWTH, APOPTOSIS AND ESTABLISHMENT OF OTHER RENAL ASSOCIATED SYNDROMES, WHICH HAVE BEEN RECOGNIZED AS ONE OF THE CRITICAL MECHANISMS FOR REGULATING FUNCTIONAL CHANGES THAT DRIVE AND MAINTAIN THE KIDNEY DISEASE PHENOTYPE. IN THIS CHAPTER, WE BRIEFLY SUMMARIZE THE EPIGENETIC MECHANISMS IN KIDNEY CELL BIOLOGY AND EPIGENETIC BASIS OF KIDNEY DEVELOPMENT, AND INTRODUCE EPIGENETIC TECHNIQUES THAT CAN BE USED IN INVESTIGATING THE MOLECULAR MECHANISM OF KIDNEY CELL BIOLOGY AND KIDNEYS DISEASES, PRIMARILY FOCUSING ON THE INTEGRATION OF DNA METHYLATION AND CHROMATIN IMMUNOPRECIPITATION TECHNOLOGIES INTO KIDNEY DISEASE ASSOCIATED STUDIES. FUTURE STUDIES USING THESE EMERGING TECHNOLOGIES WILL ELUCIDATE HOW ALTERATIONS IN THE RENAL CELL EPIGENOME COOPERATE WITH GENETIC ABERRATIONS FOR KIDNEY DISEASE INITIATION AND PROGRESSION. INCORPORATING EPIGENOMIC TESTING INTO THE CLINICAL RESEARCH IS ESSENTIAL TO FUTURE STUDIES WITH EPIGENETICS BIOMARKERS AND PRECISION MEDICINE USING EMERGING EPIGENETIC THERAPIES. 2019 13 2609 36 EPIGENETICS: A POTENTIAL KEY MECHANISM INVOLVED IN THE PATHOGENESIS OF CARDIORENAL SYNDROMES. EPIGENETICS IS DEFINED AS THE HERITABLE CHANGES IN GENE EXPRESSION PATTERNS WHICH ARE NOT DIRECTLY ENCODED BY MODIFICATIONS IN THE NUCLEOTIDE DNA SEQUENCE OF THE GENOME, INCLUDING HIGHER ORDER CHROMATIN ORGANIZATION, DNA METHYLATION, CYTOSINE MODIFICATIONS, COVALENT HISTONE TAIL MODIFICATIONS, AND SHORT NON-CODING RNA MOLECULES. RECENTLY, MUCH ATTENTION HAS BEEN PAID TO THE ROLE AND THE FUNCTION OF EPIGENETICS AND EPIMUTATIONS IN THE CELLULAR AND SUBCELLULAR PATHWAYS AND IN THE REGULATION OF GENES IN THE SETTING OF BOTH KIDNEY AND CARDIOVASCULAR DISEASE. INDEED, DEREGULATION OF HISTONE ALTERATIONS HAS BEEN HIGHLIGHTED IN A LARGE SPECTRUM OF RENAL AND CARDIAC DISEASE, INCLUDING CHRONIC AND ACUTE RENAL INJURY, RENAL AND CARDIAC FIBROSIS, CARDIAC HYPERTROPHY AND FAILURE, KIDNEY CONGENITAL ANOMALIES, RENAL HYPOXIA, AND DIABETIC RENAL COMPLICATIONS. NEVERTHELESS, THE ROLE OF EPIGENETICS IN THE PATHOGENESIS AND PATHOPHYSIOLOGY OF CARDIORENAL SYNDROMES IS CURRENTLY UNDEREXPLORED. GIVEN THE SIGNIFICANT CLINICAL RELEVANCE OF HEART-KIDNEY CROSSTALK, EFFORTS IN THE RESEARCH FOR NEW ACTION MECHANISMS CONCURRENTLY OPERATING IN BOTH PATHOLOGIES ARE THUS OF MAXIMUM INTEREST. THIS REVIEW FOCUSES ON EPIGENETIC MECHANISMS INVOLVED IN HEART AND KIDNEY DISEASE, AND THEIR POSSIBLE ROLE IN THE SETTING OF CARDIORENAL SYNDROMES. 2018 14 2333 31 EPIGENETIC REGULATION OF INFLAMMATION: THE METABOLOMICS CONNECTION. EPIGENETIC FACTORS ARE CONSIDERED THE REGULATOR OF COMPLEX MACHINERY BEHIND INFLAMMATORY DISORDERS AND SIGNIFICANTLY CONTRIBUTED TO THE EXPRESSION OF INFLAMMATION-ASSOCIATED GENES. EPIGENETIC MODIFICATIONS MODULATE VARIATION IN THE EXPRESSION PATTERN OF TARGET GENES WITHOUT AFFECTING THE DNA SEQUENCE. THE CURRENT KNOWLEDGE OF EPIGENETIC RESEARCH FOCUSED ON THEIR ROLE IN THE PATHOGENESIS OF VARIOUS INFLAMMATORY DISEASES THAT CAUSES MORBIDITY AND MORTALITY WORLDWIDE. INFLAMMATORY DISEASES ARE CATEGORIZED AS ACUTE AND CHRONIC BASED ON THE DISEASE SEVERITY AND ARE REGULATED BY THE EXPRESSION PATTERN OF VARIOUS GENES. HENCE, UNDERSTANDING THE ROLE OF EPIGENETIC MODIFICATIONS DURING INFLAMMATION PROGRESSION WILL CONTRIBUTE TO THE DISEASE OUTCOMES AND THERAPEUTIC APPROACHES. THIS REVIEW ALSO FOCUSES ON THE METABOLOMICS APPROACH ASSOCIATED WITH THE STUDY OF INFLAMMATORY DISORDERS. INFLAMMATORY RESPONSES AND METABOLIC REGULATION ARE HIGHLY INTEGRATED AND VARIOUS ADVANCED TECHNIQUES ARE ADOPTED TO STUDY THE METABOLIC SIGNATURE MOLECULES. HERE WE DISCUSS SEVERAL METABOLOMICS APPROACHES USED TO LINK INFLAMMATORY DISORDERS AND EPIGENETIC CHANGES. WE PROPOSED THAT DECIPHERING THE MECHANISM BEHIND THE INFLAMMATION-METABOLISM LOOP MAY HAVE IMMENSE IMPORTANCE IN BIOMARKERS RESEARCH AND MAY ACT AS A PRINCIPAL COMPONENT IN DRUG DISCOVERY AS WELL AS THERAPEUTIC APPLICATIONS. 2022 15 2341 28 EPIGENETIC REGULATION OF LIVER FIBROSIS. FIBROSIS IS A COMMON AND IMPORTANT PATHOLOGY ASSOCIATED WITH PROGRESSIVE CHRONIC LIVER DISEASES AND UNDERLIES THE DEVELOPMENT OF CIRRHOSIS AND HEPATOCELLULAR CARCINOMA. RESEARCH INTO THE MOLECULAR REGULATION OF FIBROSIS HAS DISCOVERED THAT IT IS UNDER THE CONTROL OF A NUMBER OF EPIGENETIC MECHANISMS INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS AND THE ACTIVITIES OF NON-CODING RNAS. A DEEPER UNDERSTANDING OF HOW EPIGENETIC REGULATORS SUCH AS DNA METHYLTRANSERASES, METHYL-DNA BINDING PROTEINS, HISTONE MODIFYING ENZYMES AND REGULATORY RNA MOLECULES IMPACT ON THE FIBROGENIC PROCESS IS EXPECTED TO RESULT IN NEW BIOMARKERS FOR DISEASE PROGRESSION AS WELL AS NOVEL THERAPEUTIC TARGETS. THE AIM OF THIS MINI-REVIEW IS TO BRIEFLY INTRODUCE THE READER TO THE MAJOR EPIGENETIC REGULATORS SO FAR IDENTIFIED AS BEING IMPLICATED IN FIBROSIS. 2015 16 2283 23 EPIGENETIC REGULATION IN FIBROSIS PROGRESS. FIBROSIS, A COMMON PROCESS OF CHRONIC INFLAMMATORY DISEASES, IS DEFINED AS A REPAIR RESPONSE DISORDER WHEN ORGANS UNDERGO CONTINUOUS DAMAGE, ULTIMATELY LEADING TO SCAR FORMATION AND FUNCTIONAL FAILURE. AROUND THE WORLD, FIBROTIC DISEASES CAUSE HIGH MORTALITY, UNFORTUNATELY, WITH LIMITED TREATMENT MEANS IN CLINICAL PRACTICE. WITH THE DEVELOPMENT AND APPLICATION OF DEEP SEQUENCING TECHNOLOGY, COMPREHENSIVELY EXPLORING THE EPIGENETIC MECHANISM IN FIBROSIS HAS BEEN ALLOWED. EXTENSIVE REMODELING OF EPIGENETICS CONTROLLING VARIOUS CELLS PHENOTYPE AND MOLECULAR MECHANISMS INVOLVED IN FIBROGENESIS WAS SUBSEQUENTLY VERIFIED. IN THIS REVIEW, WE SUMMARIZE THE REGULATORY MECHANISMS OF DNA METHYLATION, HISTONE MODIFICATION, NONCODING RNAS (NCRNAS) AND N6-METHYLADENOSINE (M6A) MODIFICATION IN ORGAN FIBROSIS, FOCUSING ON HEART, LIVER, LUNG AND KIDNEY. ADDITIONALLY, WE EMPHASIZE THE DIVERSITY OF EPIGENETICS IN THE CELLULAR AND MOLECULAR MECHANISMS RELATED TO FIBROSIS. FINALLY, THE POTENTIAL AND PROSPECT OF TARGETED THERAPY FOR FIBROSIS BASED ON EPIGENETIC IS DISCUSSED. 2021 17 2491 26 EPIGENETICS AND CARDIOVASCULAR DISEASE IN DIABETES. TYPE 2 DIABETES HAS BECOME A MAJOR HEALTH ISSUE WORLDWIDE. CHRONIC HYPERGLYCEMIA INDUCES A LOW-GRADE INFLAMMATION THAT, ON TOP OF OTHER MECHANISMS, LEADS TO ENDOTHELIAL DYSFUNCTION. MOUNTING EVIDENCE SUGGESTS THAT DNA METHYLATION, POST-TRANSLATIONAL MODIFICATIONS OF HISTONES, AND LONG NON-CODING RNAS PLAY AN IMPORTANT ROLE IN THE INITIATION, MAINTENANCE, AND PROGRESSION OF BOTH MACRO- AND MICRO-VASCULAR COMPLICATIONS OF DIABETES. LONG-TERM EXPOSURE TO HYPERGLYCEMIA INDUCES EPIGENETIC CHANGES THAT COULD BECOME IRREVERSIBLE, A PHENOMENON KNOWN AS THE 'METABOLIC MEMORY.' WHETHER EPIGENETIC-BASED THERAPIES COULD BE USED TO SLOW OR LIMIT THE PROGRESSION OF CARDIOVASCULAR DISEASE REMAINS UNCLEAR. WHILE NON-CODING RNAS ARE CURRENTLY INVESTIGATED AS POTENTIAL BIOMARKERS THAT PREDICT DIABETIC CARDIOVASCULAR DISEASE INCIDENCE AND PROGRESSION, THEIR THERAPEUTIC ROLE IS ONLY HYPOTHETICAL. IN THIS REVIEW, WE HIGHLIGHT THE LATEST FINDINGS IN EXPERIMENTAL AND CLINICAL STUDIES RELEVANT TO EPIGENETICS AND CARDIOVASCULAR DISEASE IN DIABETES. 2015 18 2413 25 EPIGENETIC SIGNALING AND RNA REGULATION IN CARDIOVASCULAR DISEASES. RNA EPIGENETICS IS PERHAPS THE MOST RECENT FIELD OF INTEREST FOR TRANSLATIONAL EPIGENETICISTS. RNA MODIFICATIONS CREATE SUCH AN EXTENSIVE NETWORK OF EPIGENETICALLY DRIVEN COMBINATIONS WHOSE ROLE IN PHYSIOLOGY AND PATHOPHYSIOLOGY IS STILL FAR FROM BEING ELUCIDATED. NOT SURPRISINGLY, SOME OF THE PLAYERS DETERMINING CHANGES IN RNA STRUCTURE ARE IN COMMON WITH THOSE INVOLVED IN DNA AND CHROMATIN STRUCTURE REGULATION, WHILE OTHER MOLECULES SEEM VERY SPECIFIC TO RNA. IT IS ENVISAGED, THEN, THAT NEW SMALL MOLECULES, ACTING SELECTIVELY ON RNA EPIGENETIC CHANGES, WILL BE REPORTED SOON, OPENING NEW THERAPEUTIC INTERVENTIONS BASED ON THE CORRECTION OF THE RNA EPIGENETIC LANDSCAPE. IN THIS REVIEW, WE SHALL SUMMARIZE SOME ASPECTS OF RNA EPIGENETICS LIMITED TO THOSE IN WHICH THE POTENTIAL CLINICAL TRANSLATABILITY TO CARDIOVASCULAR DISEASE IS EMERGING. 2020 19 2542 31 EPIGENETICS IN KIDNEY DISEASES. EPIGENETICS EXAMINES HERITABLE CHANGES IN DNA AND ITS ASSOCIATED PROTEINS EXCEPT MUTATIONS IN GENE SEQUENCE. EPIGENETIC REGULATION PLAYS FUNDAMENTAL ROLES IN KIDNEY CELL BIOLOGY THROUGH THE ACTION OF DNA METHYLATION, CHROMATIN MODIFICATION VIA EPIGENETIC REGULATORS AND NON-CODING RNA SPECIES. KIDNEY DISEASES, INCLUDING ACUTE KIDNEY INJURY, CHRONIC KIDNEY DISEASE, DIABETIC KIDNEY DISEASE AND RENAL FIBROSIS ARE MULTISTEP PROCESSES ASSOCIATED WITH NUMEROUS MOLECULAR ALTERATIONS EVEN IN INDIVIDUAL KIDNEY CELLS. EPIGENETIC ALTERATIONS, INCLUDING ANOMALOUS DNA METHYLATION, ABERRANT HISTONE ALTERATIONS AND CHANGES OF MICRORNA EXPRESSION ALL CONTRIBUTE TO KIDNEY PATHOGENESIS. THESE CHANGES ALTER THE GENOME-WIDE EPIGENETIC SIGNATURES AND DISRUPT ESSENTIAL PATHWAYS THAT PROTECT RENAL CELLS FROM UNCONTROLLED GROWTH, APOPTOSIS AND DEVELOPMENT OF OTHER RENAL ASSOCIATED SYNDROMES. MOLECULAR CHANGES IMPACT CELLULAR FUNCTION WITHIN KIDNEY CELLS AND ITS MICROENVIRONMENT TO DRIVE AND MAINTAIN DISEASE PHENOTYPE. IN THIS CHAPTER, WE BRIEFLY SUMMARIZE EPIGENETIC MECHANISMS IN FOUR KIDNEY DISEASES INCLUDING ACUTE KIDNEY INJURY, CHRONIC KIDNEY DISEASE, DIABETIC KIDNEY DISEASE AND RENAL FIBROSIS. WE PRIMARILY FOCUS ON CURRENT KNOWLEDGE ABOUT THE GENOME-WIDE PROFILING OF DNA METHYLATION AND HISTONE MODIFICATION, AND EPIGENETIC REGULATION ON SPECIFIC GENE(S) IN THE PATHOPHYSIOLOGY OF THESE DISEASES AND THE TRANSLATIONAL POTENTIAL OF IDENTIFYING NEW BIOMARKERS AND TREATMENT FOR PREVENTION AND THERAPY. INCORPORATING EPIGENOMIC TESTING INTO CLINICAL RESEARCH IS ESSENTIAL TO ELUCIDATE NOVEL EPIGENETIC BIOMARKERS AND DEVELOP PRECISION MEDICINE USING EMERGING THERAPIES. 2021 20 2154 37 EPIGENETIC MECHANISMS AND KIDNEY DISEASES. IN RECENT YEARS, MOLECULAR RESEARCH HAS BROUGHT TO LIGHT A SERIES OF MECHANISMS INVOLVED IN THE REGULATION OF GENE FUNCTION WITHOUT ALTERING THE DNA SEQUENCE. THESE MECHANISMS ARE DESCRIBED WITH THE TERM "EPIGENETICS" AND INCLUDE MODIFICATIONS IN THE STRUCTURE OF THE HUMAN GENOME, LEADING TO HERITABLE AND POTENTIALLY REVERSIBLE CHANGES IN GENE EXPRESSION. THERE IS NOW INCREASING EVIDENCE SUGGESTING THAT SEVERAL CHARACTERISTIC FEATURES OF CHRONIC KIDNEY DISEASE SUCH AS HYPERHOMOCYSTEINEMIA, SUBCLINICAL INFLAMMATION, INCREASED OXIDATIVE STRESS AND OTHERS MAY AFFECT THE HUMAN EPIGENOME. IN ADDITION, ANIMAL STUDIES HAVE SUGGESTED A POSSIBLE LINK BETWEEN NUTRITION AND ENVIRONMENTAL EXPOSURE DURING THE PERICONCEPTIONAL PERIOD AND EPIGENETIC CHANGES IN THE EXPRESSION OF MAJOR GENES IMPLICATED IN KIDNEY ORGANOGENESIS; THESE CHANGES RESULT IN A DIMINISHED NUMBER OF NEPHRONS IN THE DEVELOPING KIDNEY, WHICH PREDISPOSES TO AN INCREASED RISK FOR HYPERTENSION AND CHRONIC KIDNEY DISEASE IN FUTURE LIFE. THE UNDERSTANDING OF THE ROLE OF EPIGENETIC PHENOMENA IN THE PATHOGENESIS OF CHRONIC KIDNEY DISEASE OPENS NEW AVENUES FOR FUTURE THERAPEUTIC STRATEGIES, THROUGH THE DEVELOPMENT OF PHARMACEUTICAL AGENTS THAT TARGET DIRECTLY WITH THE CHANGES IN THE HUMAN EPIGENOME. SUCH EPIGENETIC DRUGS ARE ALREADY IN CLINICAL USE FOR THE TREATMENT OF CANCER AS WELL AS UNDER INVESTIGATION FOR THE USE IN OTHER DISEASES. THIS REVIEW WILL SUMMARIZE THE EXISTING DATA ON THE LINK BETWEEN EPIGENETIC MECHANISMS AND CHRONIC UREMIC MILIEU, AS WELL AS THE PROMISING RESULTS OF ONGOING RESEARCH IN THE FIELD OF EPIGENETIC DRUGS THAT COULD REPRESENT ADDITIONAL OPTIONS IN OUR THERAPEUTIC ARMAMENTARIUM FOR PATIENTS WITH CHRONIC KIDNEY DISEASE. 2011