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