miR‑212 promotes renal interstitial fibrosis by inhibiting hypoxia‑inducible factor 1‑α inhibitor

Zhang, Yun; Zhang, Guoxin; Che, Lishuang; Shi, Shuhan; Li, Yueting

doi:10.3892/mmr.2021.11828

Cited by 5 publications

(4 citation statements)

References 54 publications

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“…43,44 In contrast, a study showed that miR-212-5p contributed to the progression of renal interstitial fibrosis by regulating a hypoxia-inducible factor 1-α inhibitor in the kidney tissues of UUO mice. 25 In this study, we showed that miR-212-5p was abnormally expressed in obstructive kidneys and TGF-β1-induced HK-2 cells. Renal fibrosis was accelerated by miR-212-5p, whose aberrant expression was alleviated by DR3penA in vitro and in vivo.…”

Section: ■ Discussionmentioning

confidence: 65%

“…It has been widely reported that miR-212-5p plays different roles in various diseases, such as diabetes mellitus, colorectal cancer liver metastasis, and hypertension. − Even in fibrotic diseases, the functions of miR-212-5p are different. In cardiac fibrosis, miR-212-5p targets c-Myc and NLRC5, ultimately inhibiting the proliferation and activation of fibroblasts and collagen deposition. , In contrast, a study showed that miR-212-5p contributed to the progression of renal interstitial fibrosis by regulating a hypoxia-inducible factor 1-α inhibitor in the kidney tissues of UUO mice . In this study, we showed that miR-212-5p was abnormally expressed in obstructive kidneys and TGF-β1-induced HK-2 cells.…”

Section: Discussionmentioning

confidence: 66%

“…Evidence suggests that dysregulated miRNAs are involved in the pathophysiology of renal fibrosis . For example, miR-21 is significantly upregulated in human kidney diseases and experimental models and promotes fibrosis by silencing metabolic pathways. − miR-146a protects against diabetic kidney disease by attenuating fibrosis and the inflammatory response. − Studies have shown that miR-212, which belongs to the miR-132/212 family, is abnormally expressed in many diseases, such as cancer, nonalcoholic fatty liver disease, Parkinson’s disease, myocardial obstruction, and fibrosis. − However, there have been few studies of miR-212 in renal fibrosis. In this study, we screened out miR-212-5p regulated by DR3penA and determined the role and mechanism of miR-212-5p in renal fibrosis.…”

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confidence: 99%

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Novel Peptide DR3penA as a Low-Toxicity Antirenal Fibrosis Agent by Suppressing the TGF-β1/miR-212-5p/Low-Density Lipoprotein Receptor Class a Domain Containing 4/Smad Axis

Deng,

Zhang,

Zhang

et al. 2024

ACS Pharmacol. Transl. Sci.

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Renal fibrosis is a complex pathological process that contributes to the development of chronic kidney disease due to various risk factors. Conservative treatment to curb progression without dialysis or renal transplantation is widely applicable, but its effectiveness is limited. Here, the inhibitory effect of the novel peptide DR3penA (DHα-(4-pentenyl)-AlaNPQIR-NH 2 ), which was developed by our group, on renal fibrosis was assessed in cells and mice with established fibrosis and fibrosis triggered by transforming growth factor-β1 (TGF-β1), unilateral ureteral obstruction, and repeated low-dose cisplatin. DR3penA preserved renal function and ameliorated renal fibrosis at a dose approximately 100 times lower than that of captopril, which is currently used in the clinic. DR3penA also significantly reduced existing fibrosis and showed similar efficacy after subcutaneous or intraperitoneal injection. Mechanistically, DR3penA repressed TGF-β1 signaling via miR-212-5p targeting of low-density lipoprotein receptor class a domain containing 4, which interacts with Smad2/3. In addition to having good pharmacological effects, DR3penA could preferentially target injured kidneys and exhibited low toxicity in acute and chronic toxicity experiments. These results unveil the advantages of DR3penA regarding efficacy and toxicity, making it a potential candidate compound for renal fibrosis therapy.

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Section: ■ Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 66%

mentioning

confidence: 99%

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Novel Peptide DR3penA as a Low-Toxicity Antirenal Fibrosis Agent by Suppressing the TGF-β1/miR-212-5p/Low-Density Lipoprotein Receptor Class a Domain Containing 4/Smad Axis

Deng,

Zhang,

Zhang

et al. 2024

ACS Pharmacol. Transl. Sci.

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“…Furthermore, It plays a crucial role in pathological and developmental angiogenesis ( 51 ). HIF-1α was closely associated with fibrosis of tissues and intracellular oxygen metabolism ( 52 ). Macrophage HIF-1α promotes lipid uptake and proinflammatory responses contributing to AS ( 53 ).…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Tao Hong Decoction in the treatment of atherosclerosis based on network pharmacology and experimental validation

Liu²,

Feng³

et al. 2023

Front. Cardiovasc. Med.

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BackgroundAtherosclerosis (AS) has long been recognized as a cardiovascular disease and stroke risk factor. A well-known traditional Chinese medicine prescription, Tao Hong decoction (THD), has been proven effective in treating AS, but its mechanism of action is still unclear.ObjectiveTo assess the effects, explore THD’s primary mechanism for treating AS, and provide a basis for rational interpretation of its prescription compatibility.MethodsBased on network pharmacology, we evaluated the mechanism of THD on AS by data analysis, target prediction, the construction of PPI networks, and GO and KEGG analysis. AutoDockTools software to conduct Molecular docking. Then UPLC-Q-TOF-MS was used to identify significant constituents of THD. Furthermore, an AS mice model was constructed and intervened with THD. Immunofluorescence, RT-qPCR, and Western blot were used to verify the critical targets in animal experiments.ResultsThe network pharmacology results indicate that eight core targets and seven core active ingredients play an essential role in this process. The GO and KEGG analysis results suggested that the mechanism is mainly involved in Fluid shear stress and atherosclerosis and Lipid and atherosclerosis. The molecular docking results indicate a generally strong affinity. The animal experiment showed that THD reduced plaque area, increased plaque stability, and decreased the levels of inflammatory cytokines (NF-κB, IL-1α, TNF-α, IL-6, IL-18, IL-1β) in high-fat diet -induced ApoE-/-mice. Decreased levels of PTGS2, HIF-1α, VEGFA, VEGFC, FLT-4, and the phosphorylation of PI3K, AKT, and p38 were detected in the THD-treated group.ConclusionTHD plays a vital role in treating AS with multiple targets and pathways. Angiogenesis regulation, oxidative stress regulation, and immunity regulation consist of the crucial regulation cores in the mechanism. This study identified essential genes and pathways associated with the prognosis and pathogenesis of AS from new insights, demonstrating a feasible method for researching THD’s chemical basis and pharmacology.

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MicroRNA-based therapeutic strategies for chronic kidney disease and uremic cardiomyopathy

Sárközy

Csont

2022

MicroRNA

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miR‑212 promotes renal interstitial fibrosis by inhibiting hypoxia‑inducible factor 1‑α inhibitor

Cited by 5 publications

References 54 publications

Novel Peptide DR3penA as a Low-Toxicity Antirenal Fibrosis Agent by Suppressing the TGF-β1/miR-212-5p/Low-Density Lipoprotein Receptor Class a Domain Containing 4/Smad Axis

Novel Peptide DR3penA as a Low-Toxicity Antirenal Fibrosis Agent by Suppressing the TGF-β1/miR-212-5p/Low-Density Lipoprotein Receptor Class a Domain Containing 4/Smad Axis

Mechanism of Tao Hong Decoction in the treatment of atherosclerosis based on network pharmacology and experimental validation

MicroRNA-based therapeutic strategies for chronic kidney disease and uremic cardiomyopathy

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