Background:Renal angiomyolipoma (AML) is a common benign tumor of the kidney. The main complication of AML is retroperitoneal hemorrhage caused by AML rupture, which can be severe and life threatening. The risk of AML rupture used to be determined by tumor size. However, these criteria have been challenged by series of clinical studies and case reports, suggesting prediction AML rupture based on tumor size is not always reliable.Methods:The authors searched PubMed using “angiomyolipoma,” “AML,” and “rupture” and reviewed relevant studies. The authors investigated the risk factors of AML rupture using the retrieved literature. The authors also summarized current modalities to evaluate and manage AML.Results:It is established that risk of AML rupture is associated with lesion size. However, genetic abnormality, aneurysm formation, and pregnancy are also risk factors for tumor rupture. Thus, the prediction of AML rupture should be based on a more comprehensive risk assessment system. The management of renal AML and tumor rupture was also discussed in the present paper.Conclusion:The risk of AML rupture is associated with but not exclusive to lesion size. Any decision to intervene AML must be based on multiple factors including risk, symptoms, and auxiliary findings.
Bone marrow–derived mesenchymal stem cells (BMSCs) have been recently reported to play a variety of vital roles in organ and tissue damage repair, mainly via potent paracrine activity, including secreting extracellular vesicles, such as exosomes, that serve as mediators facilitating intercellular communication and reprogramming recipient cells by delivering their contents to target cells. However, the underlying mechanisms are diverse and complex, and the influencing characteristics have rarely been studied. Accordingly, we designed this study to explore the time dependence of the effects of exosomes derived from BMSCs (BMexos) on renal ischemia‐reperfusion (I/R) injury and the underlying mechanisms associated with the reperfusion time. Impressively, our study is the first to find that BMexos protected against renal I/R injury in vitro and in vivo at the very early reperfusion stages, especially 4–8 h after reperfusion in vitro and 8–16 h after reperfusion in vivo. Interestingly, we simultaneously found that endoplasmic reticulum (ER) stress was significantly suppressed following the administration of BMexos in vitro and in vivo with a similar time dependence. Additionally, we discovered that miR‐199a‐5p, which was abundant in the BMSCs, was transferred into renal tubular epithelial cells (NRK‐52E) in a time‐dependent manner and significantly inhibited I/R‐induced ER stress by targeting binding immunoglobulin protein (BIP). Cocultivation with miR‐199a‐5p‐overexpressing BMSCs amplified the suppression of ER stress and further protected against I/R injury. However, coculture with miR‐199a‐5p‐knockdown BMSCs obviously increased ER stress and reversed the BMexos‐induced protection, and silencing BIP by small interfering RNA–1098 in NRK‐52E inhibited these effects. This study provides evidence that administering BMexos at the very early reperfusion stages significantly protects against renal I/R injury, and ER stress is closely linked to this protection. These results suggest a novel therapeutic strategy during the very early reperfusion stages of renal I/R injury.—Wang, C., Zhu, G., He, W., Yin, H., Lin, F., Gou, X., Li, X. BMSCs protect against renal ischemia‐reperfusion injury by secreting exosomes loaded with miR‐199a‐5p that target BIP to inhibit endoplasmic reticulum stress at the very early reperfusion stages. FASEB J. 33, 5440–5456 (2019). http://www.fasebj.org
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