Plain-language summary
Mesenchymal stem cells from fat are usually studied for their repair potential, but their exosomes can carry the wrong message when the donor is metabolically unwell. This group isolated exosomes from perirenal fat-derived mesenchymal stem cells of healthy rats and of rats with diabetic nephropathy, then compared their effects on glomerular mesangial cells. Exosomes from the diabetic animals were markedly more pro-inflammatory and pro-fibrotic. Small RNA sequencing pointed to miR-331-3p, which was strongly elevated in those exosomes. The team showed that miR-331-3p targets TSC1, and that suppressing TSC1 activates mTORC1 signalling, driving high-glucose inflammation and fibrosis in mesangial cells; restoring TSC1 reversed the effect. In living diabetic rats, blocking miR-331-3p with an antagomir reduced kidney injury, while giving an agomir to healthy rats produced nephropathy-like damage. The authors conclude that the diabetic microenvironment reprograms perirenal fat mesenchymal stem cells towards a harmful exosomal cargo.
Key findings
- Exosomes from perirenal fat-derived mesenchymal stem cells of diabetic rats were more pro-inflammatory and pro-fibrotic than those from healthy animals.
- Sequencing identified miR-331-3p as strongly upregulated in the diabetic exosomes; it targets TSC1 and thereby activates mTORC1 signalling.
- In diabetic rats an miR-331-3p antagomir reduced renal injury, whereas an agomir induced nephropathy-like damage in healthy rats.
- The findings indicate that the metabolic state of the donor cell changes the biological message its exosomes carry. The work is preclinical.
Why this matters for lung repair
The organ here is the kidney, but the message transfers to any stem-cell-derived vesicle product: the physiological condition of the source cells shapes what their vesicles do, and a pro-fibrotic cargo can come from the same cell type that is otherwise reparative. That argues for careful donor and culture characterisation and for release testing of what a preparation actually contains. The study is preclinical and concerns a metabolic disease model, not lung therapy.
Original abstract
Perirenal fat, due to its anatomical proximity and secretory function, is intimately linked to renal physiology and is a rich source of mesenchymal stem cells (MSCs). However, the impact of exosomes from MSCs derived from perirenal fat under diabetic pathological conditions remains unclear. Exosomes were isolated from perirenal fat-derived MSCs of healthy and diabetic nephropathy (DN) rats. Their pro-inflammatory and pro-fibrotic effects on glomerular mesangial cells were assessed in vitro using ELISA, immunofluorescence, and Western blot. Differentially expressed miRNAs were identified by high-throughput sequencing. The targeting relationship between miR-331-3p and TSC1 was validated by a dual-luciferase reporter assay. Renal function and histopathology were evaluated in a diabetic rat model to assess therapeutic efficacy following miRNA modulation. MSCs from the perirenal fat of DN rats exhibited significant pro-inflammatory and pro-fibrotic properties compared to the healthy control group. miRNA sequencing revealed that miR-331-3p was significantly upregulated in exosomes from DN rats. Mechanistically, miR-331-3p overexpression promoted high glucose-induced inflammation and fibrosis in mesangial cells by directly targeting TSC1, leading to the activation of the mTOR signaling pathway. This effect was reversed by TSC1 overexpression. In vivo, administration of a miR-331-3p antagomir significantly attenuated renal injury in DN rats, whereas its agomir induced nephropathy-like damage in healthy rats. Our findings indicate that perirenal adipose-derived mesenchymal stem cells (ADMSCs) enhanced pro-inflammatory and pro-fibrotic capabilities in the diabetic microenvironment. This effect is mediated by the delivery of miR-331-3p, which promotes inflammation and fibrosis via the TSC1/mTORC1, ultimately impairing renal function in DN.
Frequently asked questions
What did this study find?
Mesenchymal stem cells from fat are usually studied for their repair potential, but their exosomes can carry the wrong message when the donor is metabolically unwell. This group isolated exosomes from perirenal fat-derived mesenchymal stem cells of healthy rats and of rats with diabetic nephropathy, then compared their effects on glomerular mesangial cells. Exosomes from the diabetic animals were markedly more pro-inflammatory and pro-fibrotic. Small RNA sequencing pointed to miR-331-3p, which was strongly elevated in those exosomes. The team showed that miR-331-3p targets TSC1, and that suppressing TSC1 activates mTORC1 signalling, driving high-glucose inflammation and fibrosis in mesangial cells; restoring TSC1 reversed the effect. In living diabetic rats, blocking miR-331-3p with an antagomir reduced kidney injury, while giving an agomir to healthy rats produced nephropathy-like damage. The authors conclude that the diabetic microenvironment reprograms perirenal fat mesenchymal stem cells towards a harmful exosomal cargo.
Was this tested in humans or in the laboratory?
This is preclinical work — the findings come from laboratory models, not from human participants.
Where can I read the original paper?
The full text lives with the publisher: https://doi.org/10.1016/j.intimp.2026.117107
Does this study prove that JuvGuard works?
No. This is an independent, peer-reviewed study on extracellular vesicles. JuvGuard references the published literature for education only. A single paper cannot establish that any product works, and nothing here is medical advice.
How to cite this paper
Zhao Yumei, Yin Hejia, Tan Hong, Zhao Yan, Shi Rou, Xing Ye et al.. Exosomes from diabetic perirenal adipose-derived MSCs promote inflammation and fibrosis in diabetic nephropathy via the miR-331-3p/TSC1/mTORC1 Axis.. International immunopharmacology. 2026, 2026-07-08. DOI: 10.1016/j.intimp.2026.117107
Source & verification
- Journal: International immunopharmacology
- Published: 8 July 2026
- DOI: 10.1016/j.intimp.2026.117107
- PubMed ID: 42419147
- Indexed via: pubmed
- MeSH terms: Animals, Exosomes, MicroRNAs, Diabetic Nephropathies, Mesenchymal Stem Cells, Tuberous Sclerosis Complex 1 Protein, Fibrosis, Rats, Male, Mechanistic Target of Rapamycin Complex 1, Rats, Sprague-Dawley, Signal Transduction