Albiflorin attenuates inflammation and apoptosis by upregulating AMPK-mediated expression of CDX2 in a mouse model of ulcerative colitis

Purpose: To investigate the mechanism underlying the ameliorative effect of albiflorin (AF) on ulcerative colitis (UC) in dextran sulphate sodium (DSS)-induced mice model. Method: Female C57BL/6 mice were administered DSS to establish a mice model of UC. After one week, the mice received AF, and the body weight and length of colon were measured. The histopathological features of colon tissues treated with hematoxylin-eosin (H & E) stain were examinedby microscopy. Expression of inflammatory cytokines and apoptosis-related proteins were determined using enzyme-linked immunosorbent assay (ELISA) and western blotting. Results: The relative abundance of goblet cells and crypts of mice were significantly reduced in DSSinduced UC mice model; furthermore, focal ulcers and mucosal damage were apparent. Moreover, treatment with DSS decreased body weight and colon length, downregulated Bcl-2 and AMPK pathwayrelated proteins, increased inflammatory cytokines levels, and upregulated Bax and cleaved caspase-3. In contrast, treatment with AF completely ameliorated DSS-induced effects. Conclusion: AF treatment attenuated DSS-induced inflammation response and apoptosis via AMPK pathway and modulation of CDX2 expression in UC mice model. Keyword: Albiflorin, Ulcerative colitis, AMPK, CDX2, Apoptosis

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Inflammatory cytokines-stimulated human muscle stem cells ameliorate ulcerative colitis via the IDO-TSG6 axis

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02118-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Shengchao Zhang ◽

Jiankai Fang ◽

Zhanhong Liu ◽

Pengbo Hou ◽

Lijuan Cao ◽

...

Keyword(s):

Ulcerative Colitis ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Inflammatory Cytokines ◽

Human Muscle ◽

Enzyme Linked Immunosorbent Assay ◽

Muscle Stem Cells ◽

Tnf Α ◽

Ifn Γ ◽

Anti Inflammatory

Abstract Background Muscle stem cells (MuSCs) are absolutely required for the formation, repair, and regeneration of skeletal muscle tissue. Increasing evidence demonstrated that tissue stem cells, especially mesenchymal stem cells (MSCs), can exert therapeutic effects on various degenerative and inflammatory disorders based on their immunoregulatory properties. Human mesenchymal stem cells (hMSCs) treated with interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were reported to possess anti-inflammatory functions by producing TNF-stimulated gene 6 (TSG-6). However, whether human muscle stem cells (hMuSCs) also possess TSG-6 mediated anti-inflammatory functions has not been explored. Methods The ulcerative colitis mouse model was established by subjecting mice to dextran sulfate sodium (DSS) in drinking water for 7 days. hMuSCs were pretreated with IFN-γ and TNF-α for 48 h and were then transplanted intravenously at day 2 of DSS administration. Body weights were monitored daily. Indoleamine 2,3-dioxygenase (IDO) and TSG-6 in hMuSCs were knocked down with short hairpin RNA (shRNA) and small interfering RNA (siRNA), respectively. Colon tissues were collected for length measurement and histopathological examination. The serum level of IL-6 in mice was measured by enzyme-linked immunosorbent assay (ELISA). Real-time PCR and Western blot analysis were performed to evaluate gene expression. Results hMuSCs treated with inflammatory factors significantly ameliorated inflammatory bowel disease (IBD) symptoms. IDO and TSG-6 were greatly upregulated and required for the beneficial effects of hMuSCs on IBD. Mechanistically, the tryptophan metabolites, kynurenine (KYN) or kynurenic acid (KYNA) produced by IDO, augmented the expression of TSG-6 through activating their common receptor aryl hydrocarbon receptor (AHR). Conclusion Inflammatory cytokines-treated hMuSCs can alleviate DSS-induced colitis through IDO-mediated TSG-6 production.

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ROLE OF ANTIOXIDANT AND MYELOPEROXIDASE LEVELS IN 7, 12-DIMETHYLBENZ [A] ANTHRACENE INDUCED EXPERIMENTAL RAT MODEL: EVIDENCE FOR OXIDATIVE DAMAGE IN ACTIVE ULCERATIVE COLITIS.

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i3.16485 ◽

2017 ◽

Vol 9 (3) ◽

pp. 282

Author(s):

P. Geetha ◽

B. Lakshman Kumar ◽

U. Indra ◽

B. Pavithra Sheetal

Keyword(s):

Ulcerative Colitis ◽

Body Weight ◽

Antioxidant Status ◽

Activity Index ◽

Disease Activity Index ◽

The Body ◽

Unknown Etiology ◽

Steady Increase ◽

Tissue Samples ◽

Significant Change

Objective: Ulcerative colitis known as inflammatory bowel disease (IBD) of unknown etiology. We examined the antioxidant and myeloperoxidase status in a murine model of 7,12-dimethylbenz[a]anthracene induced colitis to elucidate the exact mechanism behind the inflammation.Methods: Male Wistar rats were exposed to ulcerative colitis using various concentration of DMBA (7,12-Dimethylbenz[A]anthracene) were periodically analysed on 4th, 8th, 12th, 24th and 32nd week from the date of induction. To determine the disease activity index changes in body weight, food consumption, the presence of gross blood in stool and consistency of feces and diarrhea were observed. Macroscopic characters were elucidated based on clinical features of the colon and rectum using scoring pattern. Tissue inflammation status was noted through myeloperoxidase (MPO) assay. The antioxidant status in tissue samples was analysed by superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total reduced glutathione (GSH).Results: Gavage intubation of DMBA induced colitis showed significant changes from 4th week and severity on 32nd week. The body weight was gradually reduced. Macroscopic scoring showed severe scoring pattern the inflammation was significantly heavier by week 4; and by the end of 32 w, inflammation in rats was double that of the controls, tissue myeloperoxidase (MPO) activity showed the steady increase of neutrophil infiltration and inflammation rate every week. A significant change was noted in tissue antioxidant status and it showed the oxidation level. Statistically, significant change was recorded from 4th week till 32nd week.Conclusion: The conventional biochemical changes in colitis induced animal model revealed the association between the oxidative stress and ulcerative colitis.

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Dynamic Evaluation of Compound Ento-PB for the Repair of Mucosal Ulcer in Dogs With Acetic Acid-induced Experimental Colitis

10.21203/rs.3.rs-127468/v1 ◽

2020 ◽

Author(s):

Jin-hu Chen ◽

Jian-ting Zhao ◽

Zheng-yong Yu ◽

Yi-hao Che ◽

Yu-jia Wang ◽

...

Keyword(s):

Ulcerative Colitis ◽

Acetic Acid ◽

Inflammatory Cytokines ◽

Mucosal Healing ◽

Dynamic Monitoring ◽

Enzyme Linked Immunosorbent Assay ◽

Dependent Manner ◽

Expression Levels ◽

Cox 2 ◽

Anti Inflammatory

Abstract Background: Mucosal inflammation and ulcer play important roles in the pathogenesis of ulcerative colitis. As as traditional Chinese medicine compound composed of Periplaneta americana and Taraxacum mongolicum, Ento-PB is always prescribed for the treatment of ulcer and inflammatory diseases. As for the significant role of P. americana in terms of promoting mucosal healing, the compatibility of the anti-inflammatory drug T. mongolicum may enable Ento-PB to simultaneously play anti-inflammatory and promote mucosal healing effects on the treatment of UC. Therefore, this study aimed to evaluate the therapeutic potential and possible mechanism of Ento-PB for UC by establishing an acetic acid-induced colitis model in dogs.Methods: Preliminary identification to the chemical components of compound Ento-PB was carried out through high performance liquid chromatography. A cross-bred dogs model of acetic acid-induced ulcerative colitis was established to evaluate the efficacy of compound Ento-PB. The expression levels of inflammatory cytokines C-reactive protein (CRP), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-10 (IL-10) in plasma were measured by carrying out enzyme-linked immunosorbent assay (ELISA).Results: With the extension of treatment time, Ento-PB could effectively improve clinical symptoms of UC cross-bred dogs. Colonoscopy displayed that mucosal redness, swelling and congestion decreased gradually, and obviously repaired after mucosal injury. The intestinal texture was gradually clear, and the colonoscopy score gradually reduced. Histopathological examination revealed that the structure of colon was restored significantly, the infiltration of inflammatory cells was reduced, and the histological score was remarkably reduced. At the same time, the results of dynamic monitoring of inflammatory cytokines in plasma proved that Ento-PB can gradually down-regulate the activity of CRP, iNOS and COX-2, reduce the expression levels of inflammatory cytokines TNF-α and IL-1β, and gradually restore anti-inflammatory and the expression level of cytokine IL-10.Conclusions: Ento-PB reduces the level of pro-inflammatory cytokines in a dose- and time-dependent manner and inflammation, improves colon tissue lesions and the repair of intestinal mucosa after injury, and effectively increases acetic acid-induced colon inflammation in UC cross-bred dogs.

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Impact of loganin on pro-inflammatory cytokines and depression- and anxiety-like behaviors in male diabetic rats

Physiology International ◽

10.1556/2060.105.2018.2.8 ◽

2018 ◽

Vol 105 (2) ◽

pp. 116-126 ◽

Cited By ~ 2

Author(s):

M Rajabi ◽

G Mohaddes ◽

F Farajdokht ◽

S Nayebi Rad ◽

M Mesgari ◽

...

Keyword(s):

Body Weight ◽

Blood Glucose ◽

Inflammatory Cytokines ◽

Diabetic Rats ◽

Assay Method ◽

Enzyme Linked Immunosorbent Assay ◽

Depression And Anxiety ◽

Tnf Α ◽

Immobility Time ◽

Pro Inflammatory Cytokines

Behavioral disturbances are observed in most patients suffering from diabetes. According to some evidence, pro-inflammatory cytokines have a key role both in diabetes and behavioral disorders, such as anxiety and depression. In this study, the effect of chronic administration of loganin, as a bioflavonoid, was investigated on pro-inflammatory cytokines and depression- and anxiety-like behaviors in streptozotocin-induced diabetes in male Wistar rats. Blood levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were assessed by enzyme-linked immunosorbent assay method. Depression- and anxiety-like behaviors were evaluated by forced swimming test (FST), elevated plus maze (EPM), and open field test (OFT), respectively. Body weight was also measured before the interventions and after the experiments in all groups. Our findings show that loganin-treated animals had significantly lower serum concentrations of IL-6 and TNF-α compared with the diabetic group. In the EPM test, loganin treatment significantly increased the percentage of the open arm time and open arm entries. Moreover, loganin treatment significantly decreased the grooming time and restored distance traveled and center crossing in the OFT. However, it decreased immobility time in the FST. Loganin treatment also significantly restored body weight gain and attenuated blood glucose changes in the diabetic rats. These results indicate that loganin possibly alleviates depression- and anxiety-like behaviors associated with diabetes through lowering the blood glucose and pro-inflammatory cytokine levels. More research is required to show the exact mechanism of antidepressant and anxiolytic effects of loganin in diabetes.

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Effects of caffeoylxanthiazonoside on airway inflammation in an allergic asthma mice model

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v18i4.12 ◽

2021 ◽

Vol 18 (4) ◽

pp. 761-766

Author(s):

Qian Wu ◽

Hui Wang ◽

Xiaowen Che ◽

Wei Wang

Keyword(s):

Protein Expression ◽

Western Blot ◽

Airway Inflammation ◽

Allergic Asthma ◽

Inflammatory Cells ◽

Lavage Fluid ◽

The Body ◽

Enzyme Linked Immunosorbent Assay ◽

Mice Model ◽

Ifn Γ

Purpose: To investigate the inhibitory effects of caffeoylxanthiazonoside (CYT) on airway inflammation in mice and its mechanism of action. Methods: An allergic asthma mice model was established by intraperitoneal injection and aerosol nebulization with ovalbumin (OVA). After treatment with CYT, the blood and bronchoalveolar lavage fluid (BALF) were collected from the mice. The leukocytes were classified and counted with Giemsa solution. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of IgE, and IL-4, IL-5, IL-13 and IFN-γ in the BALF of mice. Lung tissues were obtained from the mice and MUC5AC protein expression was measured by western blot. Results: CYT significantly decreased the serum level of IgE in asthmatic mice. Inflammatory cells in BALF of mice were markedly reduced (p < 0.05) by CYT treatment at varying doses (10, 20, and 40 mg/kg). Treatment with CYT also significantly suppressed the cytokines of IL-4, IL-5 and IL-13 and increased the IFN-γ in the BLAF of OVA-induced allergic asthma mice (p < 0.05). Western blot results indicate that CYT treatment significantly decreased the expression of MUC5AC protein in the lung tissues of asthmatic mice. In addition, no significant effects on the body weight of the mice were found after CYT treatment. Conclusion: Caffeoylxanthiazonoside inhibits airway inflammation in allergic asthma mice by altering Th1/Th2 via re-balancing of related cytokines and downregulation of lung MUC5AC protein expression. Therefore, this compound can potentially be developed for the therapeutic management of inflammation in allergic asthma.

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Wei Chang an Pill Alleviates TNBS-induced Ulcerative Colitis Through Inhibition of EMTProcess

10.21203/rs.3.rs-139702/v1 ◽

2021 ◽

Author(s):

Yaxin Qi ◽

Lijuan Chai ◽

Min Zhang ◽

Sitong Jia ◽

Lin Wang ◽

...

Keyword(s):

Ulcerative Colitis ◽

Body Weight ◽

Epithelial Mesenchymal Transition ◽

Activity Index ◽

Pharmaceutical Preparation ◽

Damage Index ◽

The Body ◽

Active Ingredients ◽

Mesenchymal Transition ◽

Anti Inflammatory

Abstract Background: Wei Chang An pill (WCA) is a traditional Chinese pharmaceutical preparation which has been widely used to treat various gastrointestinal diseases including Ulcerative colitis (UC). The aim of our study was investigate the inhibitory effect and mechanism of WCA in the treatment of 2,4,6-trinitro-benzenesulfonic acid (TNBS)-induced UC in rats.Methods: We established the TNBS-induced UC model and then WCA was administrated orally for one week. Body weight, colon lengths, Disease Activity Index (DAI) score and Colon Mucosa Damage Index (CMDI) score were recorded. The expression of cytokines factors in LPS-stimulated THP-1 cells was recorded to evaluate the anti-inflammatory effects of WCA and its herb active ingredients. Immunohistochemistry and immunofluorescence were used to evaluate the Epithelial-Mesenchymal Transition (EMT) process in UC rats and Caco-2 cells which were induced by LPS-stimulated THP-1 cells uponWCA treatment.Results: WCA significantly decreased the body weight loss, higher DAI and CMDI score, colon length shortening and histological damage in UC rats. Furthermore, both of the activities of myeloperoxidase dismutase (MPO) and the mRNA expressions of cytokine in UC tissues were significantly inhibited. In THP-1 cells, the mRNA expressions of IP-10, TNF-α, IL-6 and IkBα were significantly suppressed by WCA or its active ingredients. In UC rats and Caco-2 cells, both of their EMT process were strongly suppressed by WCA.Conclusion: These results show that through improving inflammatory microenvironment to inhibit the EMT process, WCA retarded the development of UC in rats to play its anti-inflammatory effect.

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Impact of loganin on pro-inflammatory cytokines and depression- and anxiety-like behaviors in male diabetic rats

Physiology International ◽

10.1556/2060.105.2018.1.8 ◽

2018 ◽

Vol 105 (3) ◽

pp. 199-209 ◽

Cited By ~ 10

Author(s):

M Rajabi ◽

G Mohaddes ◽

F Farajdokht ◽

S Nayebi Rad ◽

M Mesgari ◽

...

Keyword(s):

Body Weight ◽

Blood Glucose ◽

Inflammatory Cytokines ◽

Diabetic Rats ◽

Assay Method ◽

Enzyme Linked Immunosorbent Assay ◽

Depression And Anxiety ◽

Tnf Α ◽

Immobility Time ◽

Pro Inflammatory Cytokines

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Indoleamine 2,3-dioxygenase-dependent expansion of T-regulatory cells maintains mucosal healing in ulcerative colitis

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284818793558 ◽

2018 ◽

Vol 11 ◽

pp. 175628481879355 ◽

Cited By ~ 6

Author(s):

Aleksandar Acovic ◽

Bojana Simovic Markovic ◽

Marina Gazdic ◽

Aleksandar Arsenijevic ◽

Nemanja Jovicic ◽

...

Keyword(s):

Ulcerative Colitis ◽

T Cells ◽

Inflammatory Cytokines ◽

T Regulatory Cells ◽

Serum Levels ◽

Mucosal Healing ◽

Sodium Sulphate ◽

Interleukin 17 ◽

Mice Model ◽

T Helper 1

Background: Dendritic cell (DC)-derived indolamine 2,3-dioxygenase (IDO) degrades tryptophan to kynurenine, which promotes conversion of inflammatory T cells in immunosuppressive regulatory T cells (Tregs). We analyzed the significance of the IDO:Treg axis for inducing and maintaining mucosal healing in ulcerative colitis (UC). Methods: Dextran sodium sulphate (DSS)-induced colitis in BALB/c mice (model for mucosal healing) and C57BL/6 mice (model for persistent disease) was used. Serum, fecal samples and colon-infiltrating immune cells of 65 patients with UC with mucosal healing or persistent colitis were analyzed. Results: Significantly higher serum levels of kynurenine and downregulated inflammatory cytokines were noticed in DSS-treated BALB/c mice compared with C57BL/6 mice. Increased IDO activity and attenuated capacity for antigen presentation and production of inflammatory cytokines, observed in BALB/c DCs, was followed by a significantly lower number of inflammatory T helper 1 (Th1) and Th17 cells and a notably increased number of Tregs in the colons of DSS-treated BALB/c mice. DCs and Tregs were crucially important for the maintenance of mucosal healing since their depletion aggravated colitis. Mucosal healing, followed by an increase in kynurenine and intestinal Tregs, was re-established when BALB/c DCs were transferred into DC-depleted or Treg-depleted DSS-treated BALB/c mice. This phenomenon was completely abrogated by the IDO inhibitor. Significantly higher serum and fecal levels of kynurenine, accompanied by an increased presence of intestinal Tregs, were noticed in patients with UC with mucosal healing and negatively correlated with disease severity, fecal calprotectin, colon-infiltrating interferon γ and interleukin-17-producing cells, serum and fecal levels of inflammatory cytokines. Conclusion: IDO-dependent expansion of endogenous Tregs should be further explored as a new approach for the induction and maintenance of mucosal healing in patients with UC.

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Datura Metel L. Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis and Inhibits Inflammatory Cytokines Production through TLR7/8–MyD88–NF-κB–NLRP3 Inflammasome Pathway

Molecules ◽

10.3390/molecules24112157 ◽

2019 ◽

Vol 24 (11) ◽

pp. 2157 ◽

Cited By ~ 6

Author(s):

Bing-You Yang ◽

Yan-Gang Cheng ◽

Yan Liu ◽

Yuan Liu ◽

Jin-Yan Tan ◽

...

Keyword(s):

Inflammatory Response ◽

Protective Effect ◽

Inflammatory Cytokines ◽

Nlrp3 Inflammasome ◽

Primary Response ◽

Intercellular Adhesion Molecule ◽

Enzyme Linked Immunosorbent Assay ◽

Mice Model ◽

Intercellular Adhesion Molecule 1 ◽

Datura Metel

Background: Psoriasis is a chronic, immune-mediated inflammatory skin disease, and the inflammatory response plays an important role in its development and progression. Datura metel L. is a traditional Chinese medicine that exhibited a significant therapeutic effect on psoriasis in our previous study due to its remarkable anti-inflammatory effect. Meanwhile, the mechanism underlying its effects on psoriasis is still unclear. Methods: An imiquimod-induced psoriasis-like dermatitis mouse model was constructed to evaluate the protective effect of the effective part of Datura metel L. (EPD), which was verified by evaluations of the Psoriasis Area and Severity Index (PASI) score. Hematoxylin and eosin (H&E) staining, immunohistochemical examination, enzyme-linked immunosorbent assay (ELISA), and Western blot were used to measure the inflammatory cytokines and the protein expression associated with the Toll-like receptor 7– myeloid differentiation primary response gene 88–nuclear Factor-κB–nucleotide-binding oligomerization domain (Nod)-like receptor family pyrin domain-containing 3 (TLR7/8–MyD88–NF-κB–NLRP3) inflammasome pathway. Results: EPD significantly decreased the PASI, reduced epidermal thickness, and decreased the proliferation and differentiation of epidermal cells in psoriasis-like dermatitis C57BL/6 mice induced by imiquimod (IMQ). Furthermore, EPD reduced the infiltration of CD3+ cells to psoriatic lesions, as well as ameliorated the elevations of intercellular adhesion molecule 1 (ICAM-1) and inhibited the production of imiquimod-induced inflammatory cytokines, including IL-1β, IL-2, IL-6, IL-10, IL-12, IL-17, IL-22, IL-23, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein 1 (MCP-1), and interferon-γ (IFN-γ). Besides, EPD decreased the imiquimod-induced expression levels of TLR7, TLR8, TRAF6, MyD88, p-IKKα, p-IKBα, p-NF-κB, NLRP3, apoptosis-associated speck-like protein contained a caspase recruitment domain (ASC), cysteinyl aspartate specific proteinase 1 (caspase-1), and IL-1β. Conclusion: This study demonstrated that EPD exhibited a protective effect on an imiquimod-induced psoriasis mice model by inhibiting the inflammatory response, which might be ascribed to the inhibition of the TLR7/8–MyD88–NF-κb–NLRP3 inflammasome pathway.

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MiR-203-3p inhibits the oxidative stress, inflammatory responses and apoptosis of mice podocytes induced by high glucose through regulating Sema3A expression

Open Life Sciences ◽

10.1515/biol-2020-0088 ◽

2020 ◽

Vol 15 (1) ◽

pp. 939-950

Author(s):

Jingfu Chen ◽

Qing Xu ◽

Wei Zhang ◽

YuLan Zhen ◽

Fei Cheng ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Cytokines ◽

High Glucose ◽

Renal Injury ◽

Inflammatory Responses ◽

Cell Model ◽

The Body ◽

Enzyme Linked Immunosorbent Assay ◽

Podocyte Injury

AbstractDiabetic nephropathy (DN) is the most serious long-term microvascular complication of diabetes, which mainly causes podocyte injury. Many studies have shown that microRNAs play a vital role in the development of DN. Studies have shown that miR-203-3p is involved in mesangial cell proliferation and apoptosis of DN mice. Therefore, we speculated that miR-203-3p might be related to the development of DN, but our study does not provide any evidence. In animal experiments, diabetic mice (db/db) were transfected with iR-203-3p overexpression lentiviral vectors (LV-miR-203-3p) and their control (LV-miR-con), with normal mice (db/m) being used as the control. High glucose (HG)-induced podocytes were used to construct a DN cell model in vitro. The expression levels of miR-203-3p, Semaphorin 3A (Sema3A) and inflammatory cytokines were detected by quantitative real-time polymerase chain reaction. Also, serum creatinine and blood urea nitrogen levels were used to evaluate the degree of renal injury in DN mice. Sema3A and apoptosis-related protein levels were assessed by the western blot analysis. Enzyme-linked immunosorbent assay was used to determine the different oxidative stress-related indicators and inflammatory cytokines. Flow cytometry and caspase-3 activity detection were used to analyze the degree of podocyte apoptosis. Our results suggested that the expression of miR-203-3p was lower in DN mice and in HG-induced podocytes. Overexpression of miR-203-3p reduced the body weight, blood glucose and renal injury of DN mice in vivo, as well as relieve the oxidative stress, inflammatory response and apoptosis of HG-induced podocytes in vitro. Functionally, Sema3A was a target of miR-203-3p, and Sema3A overexpression reversed the inhibitory effect of miR-203-3p on HG-induced podocyte injury. Our findings revealed that miR-203-3p alleviated the podocyte injury induced by HG via regulating Sema3A expression, suggesting that miR-203-3p might be a new therapeutic target to improve the progression of DN.

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