ArticleInternational urology and nephrology2023
MiR-449a downregulation alleviates the progression of renal interstitial fibrosis by mediating the KLF4/MFN2 axis.
Article in International urology and nephrology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 4 citations in OpenAlex.
- miR-449a modulates Alzheimer's disease pathology through regulation of Navβ2.Zoological research · 2026Article
- Cadmium exposure induces renal fibrosis by inhibiting hsa_circ_0075684/miR-363-3p/KLF4 signaling pathway.Scientific reports · 2026Article
- Optimized rAAV8 targeting acinar KLF4 ameliorates fibrosis in chronic pancreatitis via exosomes-enriched let-7s suppressing pancreatic stellate cells activation.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
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Authors and funding
8 authors at 1 institution in 1 country.
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Abstract
backgroundRenal interstitial fibrosis (RIF) seriously threatens the health of individuals. MiRNAs regulate the progression of fibrosis. Nevertheless, the detailed function of miR-449a in RIF is largely unknown.
methodsIn vitro and in vivo models of RIF were developed to evaluate the function of miR-449a. The relationship among miR-449a, KLF4, and MFN2 was explored using a dual-luciferase reporter assay and chromatin immunoprecipitation. Additionally, the pathological changes in the mice were detected using Masson staining. The mRNA and protein expressions were assessed using quantitative reverse transcription polymerase chain reaction and western blot, respectively.
resultsTGF-β1 downregulated the expressions of KLF4 and MFN2 in TCMK-1 cells, but upregulated the level of miR-449a. The downregulation of miR-449a significantly inhibited TGF-β1-induced upregulation of fibrotic proteins in TCMK-1 cells. Meanwhile, miR-449a directly targeted KLF4. Moreover, KLF4 overexpression activated MFN2 transcription and reversed TGF-β1-induced fibrosis by positively regulating MFN2. Furthermore, the downregulation of miR-449a could obviously alleviate the symptoms of RIF in mice with unilateral ureteral obstruction.
conclusionMiR-449a downregulation attenuated the development of RIF by mediating the KLF4/MFN2 axis. Therefore, miR-449a might act as a target in treating RIF.
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