MicroRNAs Offer New Hope in the Battle Against Adipose Tissue Fibrosis

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Decoding miRNA-mediated regulation of fibrotic pathways: Insights into liver fibrosis inhibition. Hypoxia-inducible factor 1-alpha (HIF-1α) enhances collagen and elastin expression by targeting LOX (lysyl oxidase), promoting liver fibrosis.

The role and therapeutic potential of miRNAs in adipose tissue fibrosis induced by high-fat diet. Transforming growth factor β (TGF-β) activates Smad3 upon binding to its receptor, and miR-140 interferes with phosphorylated SMAD3, inhibiting Smad3 express

SHANNON, CLARE, IRELAND, April 20, 2025 /EINPresswire.com/ --
A new review published in Genes & Diseases highlights the transformative role of microRNAs (miRNAs) in regulating and potentially reversing adipose tissue fibrosis, a condition closely linked to obesity, diabetes, and cardiovascular disease. Fibrosis, driven by abnormal extracellular matrix (ECM) accumulation, disrupts normal adipose tissue function and contributes to broader organ dysfunction. The review explores how miRNAs act as potent molecular regulators, capable of fine-tuning signaling pathways and gene expression patterns that influence fibrotic progression.

miRNAs, a class of small non-coding RNAs, can suppress or promote the translation of target genes involved in fibrogenic processes. Within adipose tissue, their regulation of pathways such as TGF-β/Smad, PI3K/AKT, and PPAR-γ plays a pivotal role in determining the balance between healthy tissue maintenance and pathological fibrosis. Specific miRNAs such as miR-122, miR-140, miR-150, miR-30b, and miR-155 demonstrate diverse functions, from blocking collagen synthesis to preventing the conversion of adipogenic cells into fibrogenic ones.

Of particular interest is the therapeutic application of adipose-derived stem cells (ADSCs) transfected with targeted miRNAs. These engineered cells produce a secretome—a vesicle-rich fluid carrying anti-fibrotic miRNAs—that can be delivered to affected tissues without triggering immune rejection. This approach enables precise molecular intervention, targeting key proteins like Smad3, PDGFR-β, Runx1, and PPAR-γ, which are central to fibrosis development.

The review also draws attention to miRNAs’ systemic impact, noting how alterations in adipose tissue can influence fibrosis in distant organs, including the liver, heart, and kidneys. For example, miR-410-5p, elevated in high-fat diet-induced obesity, enhances fibrosis by downregulating protective factors like Smad7 in cardiac tissue. Conversely, restoring miR-140 or delivering miR-30b can mitigate these fibrotic responses.

Ultimately, the findings underscore the potential of miRNA-based therapies as a non-invasive, targeted strategy to combat fibrosis in both adipose tissue and other organs.

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Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.
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Reference
Mei Tian, Yang Zhou, Yitong Guo, Qing Xia, Zehua Wang, Xinying Zheng, Jinze Shen, Junping Guo, Shiwei Duan, Lijun Wang, MicroRNAs in adipose tissue fibrosis: Mechanisms and therapeutic potential, Genes & Diseases, Volume 12, Issue 4, 2025, 101287, https://doi.org/10.1016/j.gendis.2024.101287

Funding Information:
Zhejiang Provincial Natural Science Foundation of China LTGD24H070006
Zhejiang Provincial Natural Science Foundation of China LTGD23H150001
Medical and Health Research Project of Zhejiang Province, China 2023KY212
Medical and Health Research Project of Zhejiang Province, China 2024KY631
Zhejiang Province Administration of Traditional Chinese Medicine (China) 2024ZL249

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