Related Experiment Video
Updated: Sep 8, 2025
Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
Published on: April 29, 2014
Renal cancer stem cell-derived sEVs impair renal function by inducing renal cell ERS and apoptosis in mice
Ruoyu Wu1, Zhiguo Chen1, Junjie Ma1
1Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background:
Cancer stem cells (CSCs) have been confirmed to participate in tumorigenesis, development, and metastasis, and to affect the local environment in normal tissues. Extracellular vesicles derived from CSCs (CSC-EVs) affect the local environment, contributing to tumor metastasis. However, the effect of small extracellular vesicles (sEVs) from renal CSCs (RCSCs) on renal function has not been studied. This study aimed to establish the impact of RCSC-sEVs on the renal function.
Methods:
RCSC-sEVs were isolated from cell lines and locally injected into C57 mouse kidneys to observe the effect of RCSC-sEVs on the renal function. 24-hour urinary protein and serum creatinine were examined for renal function evaluation. Periodic Acid-Schiff (PAS) and immunochemistry (IHC) staining were applied for investigations of the pathological changes. Western blot (WB), flow cytometry (FCM), real-time quantitative polymerase chain reaction (RT-qPCR), and TUNEL were employed to assess cell apoptosis and endoplasmic reticulum stress (ERS).
Results:
We found that RCSC-sEVs induced apoptosis and ERS in the mouse kidneys and eventually led to a decrease in the renal function. In vivo, RCSC-sEVs, applied by local injection, induced a continual increase in the 24-hour urinary protein and serum creatinine. In vitro, RCSC-sEVs induced HK2 cell ERS and apoptosis, which was caused by miR-142-3p and was confirmed by antagomir treatment. Further research showed that the miR-142-3p carried by RCSC-sEVs regulated ERp44, thus activating the PERK-CHOP pathway, which induced ERS and led to cell apoptosis.
Conclusions:
Renal function impairment during tumor development is induced not only by tumor invasion but also by RCSC-sEVs-induced renal cell apoptosis. As a natural vector of miR-142-3p, RCSC-sEVs return to the kidney cells and interfered with the expression of ERp44, inducing ERS and ultimately leading to apoptosis of normal renal cells and renal function impairment.
Insights
Small extracellular vesicles from renal cancer stem cells (RCSCs) impair kidney function by inducing apoptosis and endoplasmic reticulum stress. These RCSC-derived sEVs carry miR-142-3p, which targets ERp44, leading to renal cell damage and functional decline.
Area of Science:
- Oncology
- Nephrology
- Cell Biology
Background:
- Cancer stem cells (CSCs) drive tumor progression and metastasis.
- CSCs release extracellular vesicles (EVs) that influence the tumor microenvironment.
- The impact of small EVs (sEVs) from renal CSCs (RCSCs) on kidney function remains uninvestigated.
Purpose of the Study:
- To investigate the effect of RCSC-derived sEVs on renal function.
- To elucidate the mechanisms by which RCSC-sEVs impact kidney cells.
Main Methods:
- RCSC-sEVs were isolated and injected into mouse kidneys.
- Renal function was assessed via urinary protein and serum creatinine levels.
- Pathological changes, apoptosis, and endoplasmic reticulum stress (ERS) were analyzed using PAS, IHC, WB, FCM, RT-qPCR, and TUNEL assays.
Main Results:
- RCSC-sEVs induced apoptosis and ERS in mouse kidneys, leading to decreased renal function.
- In vivo studies showed increased urinary protein and serum creatinine after RCSC-sEV injection.
- In vitro, RCSC-sEVs induced HK2 cell ERS and apoptosis via miR-142-3p, targeting ERp44 and activating the PERK-CHOP pathway.
Conclusions:
- RCSC-sEVs contribute to renal function impairment during tumor development.
- RCSC-sEVs act as vectors for miR-142-3p, inducing ERS and apoptosis in normal renal cells.
- This process results in functional decline of the kidney.
