The Inhibition of Fibrosis and Inflammation in Obstructive Kidney Injury via the miR-122-5p/SOX2 Axis Using USC-Exos
Source abstract
Abstract
Background:Fibrosis and inflammation due to ureteropelvic junction obstruction substantially contributes to poor renal function. Urine-derived stem-cell-derived exosomes (USC-Exos) have therapeutic effects through paracrine.Methods:In vitro, the effects of USC-Exos on the biological functions of HK-2 and human umbilical vein endothelial cells were tested. Cell inflammation and fibrosis were induced by transforming growth factor-β1 and interleukin-1β, and their anti-inflammatory and antifibrotic effects were observed after exogenous addition of USC-Exos. Through high-throughput sequencing of microRNA in USC-Exos, the pathways and key microRNAs were selected. Then, the antifibrotic and anti-inflammatory effects of exosomal miR-122-5p and target genes were verified. The role of the miR-122-5p/SOX2 axis in anti-inflammatory and antifibrotic effects was verified. In vivo, a rabbit model of partial unilateral ureteral obstruction (PUUO) was established. Magnetic resonance imaging recorded the volume of the renal pelvis after modeling, and renal tissue was pathologically analyzed.Results:We examined the role of USC-Exos and their miR-122-5p content in obstructive kidney injury. These Exos exhibit antifibrotic and anti-inflammatory activities. SOX2 is the hub gene in PUUO and negatively related to renal function. We confirmed the binding relationship between miR-122-5p and SOX2. The anti-inflammatory and antifibrotic effects of miR-122-5p were inhibited, indicating that miR-122-5p has anti-inflammatory and antifibrotic effects by inhibiting SOX2 expression. In vivo, the PUUO group showed typical obstructive kidney injury after modeling. After USC-Exo treatment, the shape of the renal pelvis shown a remarkable improvement, and inflammation and fibrosis decreased.Conclusions:We confirmed that miR-122-5p from USC-Exos targeting SOX2 is a new molecular target for postoperative recovery treatment of obstructive kidney injury.
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Research context
OpenAlex topics: Extracellular vesicles in disease · Renal and Vascular Pathologies · Pediatric Urology and Nephrology Studies
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Pediatric Surgery, The Sixth Hospital Affiliated to Harbin Medical University, Harbin Medical University, No.998 Aiying Street, Harbin 150027, Heilongjiang, China.
Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University,Hangzhou 310024, Zhejiang, China.
Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, Zhejiang, China.
Laboratory of Systems Immunology, Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou 310024, Zhejiang, China.
Department of General Surgery, The Second Hospital Affiliated to Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou 310022, Zhejiang, China.
Department of General Surgery, The Second Hospital Affiliated to Anhui Medical University, No. 678 Furong Road, Hefei 230031, Anhui, China.
Funding
National Natural Science Foundation of China · Pediatric Teacher Funding Project of Harbin Medical University · Specialized Research Fund for the Doctoral Program of Higher Education of China · the Key Research and Development Plan of Heilongjiang Province · Open Project Program of Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China · Ministry of Education
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