Enhancing miR-19a/b induced cardiomyocyte proliferation in infarcted hearts by alleviating oxidant stress and controlling miR-19 release.

Fully restoring the lost population of cardiomyocytes and heart function remains the greatest challenge in cardiac repair post myocardial infarction. In this study, a pioneered highly ROS-eliminating hydrogel was designed to enhance miR-19a/b induced cardiomyocyte proliferation by lowering the oxidative stress and continuously releasing miR-19a/b in infarcted myocardium in situ. In vivo lineage tracing revealed that ∼20.47 % of adult cardiomyocytes at the injected sites underwent cell division in MI mice. In MI pig the infarcted size was significantly reduced from 40 % to 18 %, and thereby marked improvement of cardiac function and increased muscle mass. Most importantly, our treatment solved the challenge of animal death--all the treated pigs managed to live until their hearts were harvested at day 50. Therefore, our strategy provides clinical conversion advantages and safety for healing damaged hearts and restoring heart function post MI, which will be a powerful tool to battle cardiovascular diseases in patients.

MiRNA expression affects survival in patients with obstructive sleep apnea and metastatic colorectal cancer.

Introduction: The relationship between obstructive sleep apnea (OSA) and cancer has been recognized for some time now. However, little is known about the mechanisms by which sleep apnea promotes tumorigenesis and the impact of OSA on survival after cancer diagnosis. In the last few years, research has focused on the exploration of different biomarkers to understand the mechanisms underlying this relationship and miRNAs, non-coding single strands of about 22 nucleotides that post-transcriptionally regulate gene expression, have emerged as possible actors of this process.The aim of the study was to evaluate the impact of OSA on survival of metastatic colorectal cancer (mCRC) patients based on the expression of specific miRNAs. Methods: The expression of 6 miRNAs, respectively miR-21, miR-23b, miR-26a, miR-27b, miR-145 and miR-210, was analyzed by qRT-PCR in patients' sera. Response to first-line therapy, Kaplan-Meier curves of overall and progression-free survival were used to evaluate survival in mCRC patients with and without OSA stratified for the expression of miRNAs. Results: The expression of miR-21, miR-23b, miR-26a and miR-210 was significantly upregulated in mCRCs with OSA compared to no OSA. In mCRC patients with OSA and increasing expression of miR-21, miR-23b, miR-26a and miR-210 risk of progression after first-line therapy was higher and both overall and progression-free survival were significantly worst. Conversely, as miR-27b and miR-145 expression increased, the life expectancy of patients diagnosed with OSA and mCRC improved markedly. Conclusions: This study highlights the relevance of specific miRNAs on OSA in mCRCs and their significance as non-invasive biomarkers in predicting the prognosis in patients with mCRC and OSA.

The relationship between microRNAs and COVID-19 complications.

Over the past three years, since the onset of COVID-19, several scientific studies have concentrated on understanding susceptibility to the virus, the progression of the illness, and possible long-term complexity. COVID-19 is broadly recognized with effects on multiple systems in the body, and various factors related to society, medicine, and genetics/epigenetics may contribute to the intensity and results of the disease. Additionally, a SARS-CoV-2 infection can activate pathological activities and expedite the emergence of existing health issues into clinical problems. Forming easily accessible, distinctive, and permeable biomarkers is essential for categorizing patients, preventing the disease, predicting its course, and tailoring treatments for COVID-19 individually. One promising candidate for such biomarkers is microRNAs, which could serve various purposes in understanding diverse forms of COVID-19, including susceptibility, intensity, disease progression, outcomes, and potential therapeutic options. This review provides an overview of the most significant findings related to the involvement of microRNAs in COVID-19 pathogenesis. Furthermore, it explores the function of microRNAs in a broad span of effects that may arise from accompanying or underlying health status. It underscores the value of comprehending how diverse conditions, such as neurological disorders, diabetes, cardiovascular diseases, and obesity, interact with COVID-19.

Increasing MicroRNA Abundance by Targeting Biogenesis from the Primary Transcript with Steric-Blocking Antisense Oligonucleotides.

MicroRNAs (miRNAs) are regulators of gene expression, and their dysregulation is linked to cancer and other diseases, making them important therapeutic targets. Several strategies for targeting and modulating miRNA activity are being explored. For example, steric blocking antisense oligonucleotides (ASOs) can reduce miRNA activity by either blocking binding sites on specific mRNAs or base-pairing to the miRNA itself to prevent its interaction with the target mRNAs. ASOs have been less explored as a tool to elevate miRNA levels, which could also be beneficial for treating disease. In this study, using the PKD1/miR-1225 gene locus as an example, where miR-1225 is located within a PKD1 intron, we demonstrate an ASO-based strategy that increases miRNA abundance by enhancing biogenesis from the primary miRNA transcript. Disruptions in PKD1 and miR-1225 are associated with autosomal dominant polycystic kidney disease (ADPKD) and various cancers, respectively, making them important therapeutic targets. We investigated PKD1 sequence variants reported in ADPKD that are located within the sequence shared by miR-1225 and PKD1, and identified one that causes a reduction in miR-1225 without affecting PKD1. We show that this reduction in miR-1225 can be recovered by treatment with a steric-blocking ASO. The ASO-induced increase in miR-1225 correlates with a decrease in the abundance of predicted miR-1225 cellular mRNA targets. This study demonstrates that miRNA abundance can be elevated using ASOs targeted to the primary transcript. This steric-blocking ASO-based approach has broad potential application as a therapeutic strategy for diseases that could be treated by modulating miRNA biogenesis.

Therapeutic potential of xtr-miR-22-3p from Plastrum testudinis in acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is marked by a block at the promyelocyte stage. Treatments like ATRA and ATO face resistance and relapse issues. Plastrum testudinis, a traditional Chinese medicine, may offer therapeutic potential. This study investigated xtr-miR-22-3p from P. testudinis for treating APL. High expression of xtr-miR-22-3p was confirmed, with target prediction indicating interactions with key genes, including PML. xtr-miR-22-3p reduced HL-60 leukemia cell growth, altered the cell cycle, and selectively inhibited HL-60 proliferation while promoting BMSC growth, suggesting its potential as a targeted APL therapy.

Regulation mechanism of microRNAs in cardiac cells-derived exosomes in cell crosstalk.

The heart is a multicellular system, and the intercellular crosstalk mechanism is very important for the growth and development of the heart and even the organs, tissues, and cells at a distance. As a kind of extracellular vesicle, exosomes are released by different types of cells and can carry specific genetic material, endosomal proteins, cytokines, etc., which are the main material basis for mediating cell crosstalk mechanism. Among them, microRNA carried by cardiac cells-derived exosomes have highly conserved sequences and play a key role in regulating the function of organs, tissues, and cells related to cardiovascular diseases and their complications and comorbidities, which have attracted extensive attention in the medical community in recent years. Following up on the latest research progress at home and abroad, this review systematically summarized the regulatory role of microRNA from cardiac cells-derived exosomes in various cell crosstalk, including not only cardiac cells (including cardiomyocytes, fibroblasts, myofibroblast, cardiac progenitor cells, cardiac microvascular endothelial cells, cardiosphere-derived cells, etc.) but also tumor cells, bone marrow progenitor cells, and other tissue cells, in order to provide a reference for the prevention and treatment of cardiovascular diseases and their complications and comorbidities.

MicroRNAs as promising diagnostic and prognostic markers for the human genitourinary cancer.

Genitourinary cancer (GUC) represents more than one fifth of all human cancers. This makes the development of approaches to its early diagnosis an important task of modern biomedicine. Circulating microRNAs, short (17-25 nucleotides) non-coding RNA molecules found in human biological fluids and performing a regulatory role in the cell, are considered as promising diagnostic and prognostic biomarkers of cancers, including GUC. In this review we have considered the current state of research aimed at assessing microRNAs as biomarkers of such human GUC types as malignant tumors of the bladder, kidney, prostate, testicles, ovaries, and cervix. A special attention has been paid to studies devoted to the identification of microRNAs in urine as a surrogate "liquid biopsy" that may provide the simplest and cheapest approach to mass non-invasive screening of human GUC. The use of microRNA panels instead of single types of microRNA generally leads to higher sensitivity and specificity of the developed diagnostic tests. However, to date, work on the microRNAs assessment as biomarkers of human GUC is still of a research nature, and the further introduction of diagnostic tests based on microRNAs into practice requires successful clinical trials.

Clinical applications of circulating biomarkers in non-small cell lung cancer.

Despite recent advances in cancer diagnostics and treatment, the mortality associated with lung cancer is still the highest in the world. Late-stage diagnosis, often accompanied by metastasis, is a major contributor to the high mortality rates, emphasizing the urgent need for reliable and readily accessible diagnostic tools that can detect biomarkers unique to lung cancer. Circulating factors, such as circulating tumor DNA and extracellular vesicles, from liquid biopsy have been recognized as diagnostic or prognostic markers in lung cancer. Numerous clinical studies are currently underway to investigate the potential of circulating tumor DNA, circulating tumor RNA, exosomes, and exosomal microRNA within the context of lung cancer. Those clinical studies aim to address the poor diagnostics and limited treatment options for lung cancer, with the ultimate goal of developing clinical markers and personalized therapies. In this review, we discuss the roles of each circulating factor, its current research status, and ongoing clinical studies of circulating factors in non-small cell lung cancer. Additionally, we discuss the circulating factors specifically found in lung cancer stem cells and examine approved diagnostic assays designed to detect circulating biomarkers in lung cancer patients.

Advances in application of hypoxia-preconditioned mesenchymal stem cell-derived exosomes.

Mesenchymal stem cells (MSCs) primarily secrete physiologically functional exosomes via paracrine effects that act on various adjacent and distant cells, thus exerting their therapeutic effects. In recent years, hypoxic preconditioning, as a novel MSC culture mode, has emerged as a research hotspot. Many previous studies have shown the role and underlying regulatory mechanisms of hypoxic preconditioning in various diseases, which has provided sufficient reference materials for the MSC research field. Therefore, this review summarizes the progress in application of hypoxia-preconditioned MSC-derived exosomes that substantially increases and improves the biological activity of specific molecules, such as microRNA.

Deep Learning Based Micro-RNA Analysis of Lipopolysaccharide Exposed Periodontal Ligament Stem Cells Exosomes Reveal Apoptotic and Inflammasome Derived Pathway Activation.

Background: The production of inflammatory factors in periodontium is increased by LPS, particularly from P. gingivalis, and the damage to periodontal tissues is exacerbated. Exosomes from periodontal ligament stem cells change regeneration and repair brought on by bacterial LPS. MiRNAs are carried by exosomes to recipient cells to affect epigenetic functions. Thus, this study aims to utilize deep learning algorithms to uncover novel micro-RNA biomarkers in bacterial LPS-exposed PDLSC stem cells to understand the activation pathway. Methods: Using NCBI GEO DATA SET GSE163489, the most differentially expressed micro RNAs were found to differ between healthy and LPS-induced PDLSC cells. Deep learning analysis, employing a Random Forest, Artificial Neural Network c, a Support Vector Machine (SVM), and a Linear Regression model implemented within the orange data mining toolkit, identified novel microRNA biomarkers. The orange data mining toolkit was utilized for deep learning analysis of microRNA expression data, providing a user-friendly environment for machine learning tasks like classification, regression, and clustering. Results: Random Forest emerged as the superior model, achieving the highest R 2 score (.985) and the lowest RMSE (0.189) compared to Neural Networks (R 2 = .952, RMSE = 0.332), Linear Regression (R 2 = .949, RMSE = 0.343), and SVM (R 2 = .931, RMSE = 0.398). This suggests its superior ability to capture the underlying patterns in the microRNA expression data. Given its robust performance, Random Forest holds promise for identifying novel biomarkers, developing more accurate diagnostic tools, and potentially guiding the stratification of patients for targeted therapeutic interventions in periodontal disease. Conclusion: The current study utilizes deep learning analysis of microRNA expression data to identify novel biomarkers associated with inflammasome activation and anti-apoptotic pathways. These findings hold promise for guiding the development of novel therapeutic strategies for periodontal disease. However, future studies are warranted to validate these biomarkers using independent datasets and experimental methods.

Evaluation of MicroRNA 145 and MicroRNA 155 as Markers of Cardiovascular Risk in Chronic Kidney Disease.

Background Chronic kidney disease (CKD) leads to a progressive decline in renal function, primarily due to deteriorating kidney structures. Vascular calcification is a key effect of CKD. MicroRNAs (miRNAs) play a significant role in the onset and progression of both cardiovascular illness and CKD. Aim The aim of this study was to compare biomarkers of endothelial dysfunction, 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone (iPTH), miRNA 155, and miRNA 145, in patients with CKD versus controls. Methods We recruited 60 patients with CKD and 60 controls. All participants underwent brachial artery flow-mediated dilatation (FMD). Asymmetric dimethylarginine (ADMA) levels were measured using ELISA. Levels of miRNA 145 and miRNA 155 were quantified using real-time polymerase chain reaction (PCR). Results Serum levels of miRNA 145, miRNA 155, 25(OH)D, and FMD were significantly lower in CKD patients compared to controls. Conversely, serum ADMA and iPTH levels were significantly higher in CKD patients. There was a significant negative association between miRNA 145, miRNA 155, FMD, and 25(OH)D with ADMA and iPTH. Additionally, miRNA 145, miRNA 155, FMD, and 25(OH)D showed a significant positive correlation with estimated glomerular filtration rate (eGFR) and with each other. Conclusion Lower levels of miRNA 145 and miRNA 155 and increased endothelial dysfunction correlate with CKD severity, suggesting an accelerated risk for cardiovascular disease (CVD).

Plasma microRNA-15a/16-1 serves as a non-invasive indicator of liver fibrosis severity in individuals with chronic hepatitis B.

Background: The lack of effective non-invasive diagnostic methods for liver fibrosis hinders timely treatment for chronic hepatitis B (CHB) patients, leading to the progression of advanced liver disease. Circulating microRNAs offer a non-invasive approach to fibrosis assessment. MicroRNA-15a/16-1 (miR-15a/16) was reported to be implicated in fibrosis development, but the role of plasma miR-15a/16 in liver fibrosis assessment remains poorly understood. This study explored the importance of plasma miR-15a/16 in assessing liver fibrosis severity of CHB patients. Methods: Quantitative PCR was utilized to measure the levels of plasma miR-15a/16 in 435 patients with CHB and 74 healthy controls. We assessed the correlation between plasma miR-15a/16 levels and liver fibrosis and cirrhosis using Pearson correlation coefficients, multivariate linear and logistic regression models, and smooth curve fitting. Utilizing the receiver operating characteristic (ROC) curve, we examined the diagnostic potential of plasma miR-15a/16 in severe fibrosis and cirrhosis. Results: Plasma levels of miR-15a/16 in patients with CHB were significantly reduced compared to those in healthy controls. In the CHB cohort, levels were notably decreased in individuals with severe fibrosis or cirrhosis compared to those without severe fibrosis or cirrhosis. Plasma miR-15a/16 levels exhibited a negative relationship with the severity of liver fibrosis, gradually decreasing as the histological fibrosis stage progressed from S0 to S4. Reduced levels of plasma miR-15a/16 were linked to an elevated risk of severe liver fibrosis (miR-15a: odds ratio [OR] = 0.243; 95 % confidence interval [CI]: 0.138, 0.427; miR-16: OR = 0.201; 95 % CI: 0.097, 0.417) and cirrhosis (miR-15a: OR = 0.153; 95 % CI: 0.079, 0.298; miR-16: OR = 0.064; 95 % CI: 0.025, 0.162). MiR-15a achieved an area under the ROC curve of 0.886 and 0.832 for detecting moderate-to-severe fibrosis (S2-S4) and cirrhosis, respectively. MiR-16 demonstrated similar diagnostic values. Conclusion: Plasma miR-15a/16 levels were negatively correlated with the severity of liver fibrosis in CHB patients and could serve as a new non-invasive indicator in evaluating liver fibrosis.

Flavonoids as modulators of miRNA expression in pancreatic cancer: Pathways, Mechanisms, And Therapeutic Potential.

Pancreatic cancer (PC) is a complex malignancy, distinguished by its aggressive characteristics and unfavorable prognosis. Recent developments in understanding the molecular foundations of this disease have brought attention to the noteworthy involvement of microRNAs (miRNAs) in disease development, advancement, and treatment resistance. The anticancer capabilities of flavonoids, which are a wide range of phytochemicals present in fruits and vegetables, have attracted considerable interest because of their ability to regulate miRNA expression. This review provides the effects of flavonoids on miRNA expression in PC, explains the underlying processes, and explores the possible therapeutic benefits of flavonoid-based therapies. Flavonoids inhibit PC cell proliferation, induce apoptosis, and enhance chemosensitivity via the modulation of miRNAs involved in carcinogenesis. Additionally, this review emphasizes the significance of certain miRNAs as targets of flavonoid action. These miRNAs have a role in regulating important signaling pathways such as the phosphoinositide-3-kinase-protein kinase B/Protein kinase B (Akt), mitogen activated protein kinase (MAPK), Janus kinase/signal transducers and activators of transcription (JAK/STAT), and Wnt/ß-catenin pathways. This review aims to consolidate current knowledge on the interaction between flavonoids and miRNAs in PC, providing a comprehensive analysis of how flavonoid-mediated modulation of miRNA expression could influence cancer progression and therapy. It highlights the use of flavonoid nanoformulations to enhance stability, increase absorption, and maximize anti-PC activity, improving patient outcomes. The review calls for further research to optimize the use of flavonoid nanoformulations in clinical trials, leading to innovative treatment strategies and more effective approaches for PC.

Ingenious dual-circle DNA walker-mediated electrochemical biosensor for rapid and ultrasensitive detection of microRNA.

In this work, an ingenious dual-circle DNA walker (DCDW) with pretty fast walking speed and high amplification efficiency was developed for rapid and ultrasensitive electrochemical detection of microRNA-221 (miRNA-221) related to liver cancer, combined with the toehold-mediated strand-displacement reactions (TSDRs). Impressively, compared with the traditional DNA walker, the DCDW with unique double-stranded interlocked DNA nanostructure not only possesses higher stability, flexibility, and anti-entanglement ability, but also enables more functional domain in a smaller area, thereby enhancing the local concentration, which can greatly improve the working efficiency. As a validation, the electrochemical biosensor realized rapid and ultrasensitive detection of miRNA-221 with a reaction time of 15 min and detection limit down to 1.9 aM, and had been applied in MHCC97L and HeLa cancer cell lysates, thus providing an innovative insight to design intelligent functional interlocked DNA walkers for ultimate application in the construction of biosensing platform and miRNA detection in biological sample.

Safety and Tolerability of Anti-microRNA-328 Ophthalmic Solution, SHJ002, in Pediatric Subjects: First-in-Human Clinical Study.

PURPOSE: microRNA-328 has been reported as a risk factor for myopia development. SHJ002 is an antisense for microRNA-328, and SHJ002 was formulated as ophthalmic solution for a novel microRNA therapy. We aimed to investigate the safety and tolerability of SHJ002 ophthalmic solution in children. METHODS: This was a single-center, open-label, first-in-human trial in healthy children (NCT04928144). All subjects received the study medication. The trial had 2 stages. Stage 1 was an intrasubject dose-escalation study, and stage 2 was the highest tolerable dose study. The SHJ002 ophthalmic solution was instilled in a randomly selected study eye in each participant, whereas the other untreated eye served as a negative control. Three participants were assigned to stage 1, and they received eye drops of 3 concentrations (0.025%, 0.08%, and 0.25%), each of which was used for 3 consecutive days. The highest tolerable dose from stage 1 was used in stage 2 where another 9 participants were recruited for 28-day treatment. Ocular assessments, physical examination, and vital signs were measured to evaluate safety and tolerability. FINDINGS: There were 4 boys and 8 girls with a mean age of 12.3 years and a SD of 1.56. All participants were Asians. All 3 concentrations used in stage 1 were well tolerated, and the dose of 0.25% was used in stage 2. There were no reports of discomfort. There was only 1 mild adverse event (punctate keratitis) in the untreated eye in 1 participant, which was deemed as "unrelated to study drug." IMPLICATIONS: SHJ002 is a novel microRNA therapy that uses eye drop instillation. SHJ002 ophthalmic solution is generally safe and tolerable, which warrants further investigations in Phase II and III trials. CLINICALTRIALS: gov identifier: NCT04928144.

MicroRNAs as promising drug delivery target to ameliorate chronic obstructive pulmonary disease using nano-carriers: a comprehensive review.

Chronic obstructive pulmonary disease (COPD) is a deteriorating condition triggered by various factors, such as smoking, free radicals, and air pollution. This worsening disease is characterized by narrowing and thickening of airways, painful cough, and dyspnea. In COPD, numerous genes as well as microRNA (miRNA) play a significant role in the pathogenesis of the disease. Many in vivo and in vitro studies suggest that upregulation or suppression of certain miRNAs are effective treatment options for COPD. They have been proven to be more beneficial than the current symptomatic treatments, such as bronchodilators and corticosteroids. MiRNAs play a crucial role in immune cell development and regulate inflammatory responses in various tissues. MiRNA treatment thus allows for precision therapy with improved outcomes. Nanoparticle drug delivery systems such as polymeric nanoparticles, inorganic nanoparticles, dendrimers, polymeric micelles, and liposomes are an efficient method to ensure the biodistribution of the miRNAs to the target site. Identification of the right nanoparticle depending on the requirements and compatibility is essential for achieving maximum therapeutic effect. In this review, we offer a thorough comprehension of the pathology and genetics of COPD and the significance of miRNAs concerning various pathologies of the lung, as potential targets for treating the disease. The present review offers the latest insights into the nanoparticle drug delivery systems that can efficiently carry and deliver miRNA or antagomirs to the specific target site and hence help in effective management of COPD.

MicroRNA-21 (miR-21) in breast cancer: From apoptosis dysregulation to therapeutic opportunities.

Breast cancer, a pervasive and complex disease, continues to pose significant challenges in the field of oncology. Its heterogeneous nature and diverse molecular profiles necessitate a nuanced understanding of the underlying mechanisms driving tumorigenesis and progression. MicroRNA-21 (miR-21) has emerged as a crucial player in breast cancer development and progression by modulating apoptosis, a programmed cell death mechanism that eliminates aberrant cells. MiR-21 overexpression is a hallmark of breast cancer, and it is associated with poor prognosis and resistance to conventional therapies. This miRNA exerts its oncogenic effects by targeting various pro-apoptotic genes, including Fas ligand (FasL), programmed cell death protein 4 (PDCD4), and phosphatase and tensin homolog (PTEN). By suppressing these genes, miR-21 promotes breast cancer cell survival, proliferation, invasion, and metastasis. The identification of miR-21 as a critical regulator of apoptosis in breast cancer has opened new avenues for therapeutic intervention. This review investigates the intricate mechanisms through which miR-21 influences apoptosis, offering insights into the molecular pathways and signaling cascades involved. The dysregulation of apoptosis is a hallmark of cancer, and understanding the role of miR-21 in this context holds immense therapeutic potential. Additionally, the review highlights the clinical significance of miR-21 as a diagnostic and prognostic biomarker in breast cancer, underscoring its potential as a therapeutic target.

Harnessing the potential of mesenchymal stem cells-derived exosomes in degenerative diseases.

Mesenchymal stem cells (MSCs) have gained attention as a promising therapeutic approach in both preclinical and clinical osteoarthritis (OA) settings. Various joint cell types, such as chondrocytes, synovial fibroblasts, osteoblasts, and tenocytes, can produce and release extracellular vesicles (EVs), which subsequently influence the biological activities of recipient cells. Recently, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have shown the potential to modulate various physiological and pathological processes through the modulation of cellular differentiation, immune responses, and tissue repair. This review explores the roles and therapeutic potential of MSC-EVs in OA and rheumatoid arthritis, cardiovascular disease, age-related macular degeneration, Alzheimer's disease, and other degenerative diseases. Notably, we provide a comprehensive summary of exosome biogenesis, microRNA composition, mechanisms of intercellular transfer, and their evolving role in the highlight of exosome-based treatments in both preclinical and clinical avenues.

Tofogliflozin attenuates renal lipid deposition and inflammation via PPARα upregulation mediated by miR-21a impairment in diet-induced steatohepatitic mice.

We previously demonstrated hepatic, cardiac, and skin inflammation in a high-fat diet-induced steatotic liver disease (SLD) model. However, the molecular mechanism in the kidneys in this model remains unclear. It has been recently reported that SGLT2 inhibitors improve chronic kidney disease (CKD). Therefore, we used this model to evaluate the effects of tofogliflozin on renal lipid metabolism and inflammation. Male 8-10-week-old C57Bl/6 mice were fed a high-fat/high-cholesterol/high-sucrose/bile acid (HF/HC/HS/BA) diet with 0.015% tofogliflozin (Tofo group) or an HF/HC/HS/BA diet alone (SLD group). After eight weeks, serum lipid profiles, histology, lipid content, and mRNA/microRNA and protein expression levels in the kidney were examined. The Tofo group showed significant reductions in body (26.9 ± 0.9 vs. 24.5 ± 1.0 g; p < 0.001) and kidney weight compared to those of the SLD group. Renal cholesterol (9.1 ± 1.6 vs. 7.5 ± 0.7 mg/g; p < 0.05) and non-esterified fatty acid (NEFA) (12.0 ± 3.0 vs. 8.4 ± 1.5 µEq/g; p < 0.01) were significantly decreased in the Tofo group. Transmission electron microscopy revealed the presence of fewer lipid droplets. mRNA sequencing analysis revealed that fatty acid metabolism-related genes were upregulated and NFκB signaling pathway-related genes were downregulated in the Tofo group. MicroRNA sequencing analysis indicated that miR-21a was downregulated and miR-204 was upregulated in the Tofo group. Notably, the expression of PPARα, which has been known to be negatively regulated by miR-21, was significantly increased, leading to enhancing ß-oxidation genes, Acox1 and Cpt1 in the Tofo group. Tofogliflozin decreased renal cholesterol and NEFA levels and improved inflammation through the regulation of PPARα and miR-21a.