Xing Yanan, An Yanru, Tian Tian, Pu Li, Lu Zhigang, Liang Ning, Liu Longqi, Shang Zhouchun
College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
BGI Research, Shenzhen, 518083, China.
Biochem Biophys Rep. 2025 Jun 23;43:102087. doi: 10.1016/j.bbrep.2025.102087. eCollection 2025 Sep.
A deeper understanding of the cellular and molecular pathology pathways of renal fibrosis in lupus nephritis (LN) is essential for the accurate disease assessment and the development of novel therapeutic strategies. In this study, we employed advanced spatial transcriptomics technique to elucidate the underlying mechanism of renal fibrosis in mouse kidneys. By establishing single-nuclei and spatial transcriptomic maps for LN and control kidneys, we identified a significant activation and proliferation of fibroblasts predominantly in the inner stripe of outer medulla (ISOM) region and pinpointed a set of specific gene signatures associated with fibrosis. Furthermore, we discovered a class of pro-fibrotic macrophage subtype, Lyz2 macrophage, that promotes myofibroblast activation. We elucidated the intricate molecular interplay mechanisms involved in this process. Our study also delved into the glomerular region, revealed disease-induced alterations in gene expression and identified potential novel therapeutic targets.
深入了解狼疮性肾炎（LN）中肾纤维化的细胞和分子病理途径对于准确的疾病评估和新型治疗策略的开发至关重要。在本研究中，我们采用先进的空间转录组学技术来阐明小鼠肾脏中肾纤维化的潜在机制。通过建立LN和对照肾脏的单核和空间转录组图谱，我们发现主要在外髓质内带（ISOM）区域的成纤维细胞有显著激活和增殖，并确定了一组与纤维化相关的特定基因特征。此外，我们发现了一类促纤维化巨噬细胞亚型，即Lyz2巨噬细胞，它可促进肌成纤维细胞激活。我们阐明了该过程中涉及的复杂分子相互作用机制。我们的研究还深入探讨了肾小球区域，揭示了疾病诱导的基因表达变化，并确定了潜在的新型治疗靶点。
