Garantziotis Panagiotis, Doumas Stavros A P, Boletis Ioannis, Frangou Eleni
Department of Clinical Immunology and Rheumatology, Medical University Hannover, 30625 Hannover, Germany.
Lab of Autoimmunity and Inflammation, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece.
J Clin Med. 2021 May 24;10(11):2262. doi: 10.3390/jcm10112262.
Despite improvements in understanding the pathogenic mechanisms of primary glomerular diseases, therapy still remains nonspecific. We sought to identify novel therapies targeting kidney-intrinsic injury of distinct primary glomerulonephritides through computational systems biology approaches. We defined the unique transcriptional landscape within kidneys from patients with focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), immunoglobulin A nephropathy (IgAN), membranous nephropathy (MN) and thin basement membrane nephropathy (TBMN). Differentially expressed genes were functionally annotated with enrichment analysis, and distinct biological processes and pathways implicated in each primary glomerular disease were uncovered. Finally, we identified novel drugs and small-molecule compounds that may reverse each glomerulonephritis phenotype, suggesting they should be further tested as precise therapy in primary glomerular diseases.
尽管在理解原发性肾小球疾病的致病机制方面有所进步，但治疗方法仍然缺乏特异性。我们试图通过计算系统生物学方法，确定针对不同原发性肾小球肾炎肾脏固有损伤的新型治疗方法。我们定义了局灶节段性肾小球硬化症（FSGS）、微小病变肾病（MCD）、免疫球蛋白A肾病（IgAN）、膜性肾病（MN）和薄基底膜肾病（TBMN）患者肾脏内独特的转录图谱。通过富集分析对差异表达基因进行功能注释，揭示了每种原发性肾小球疾病所涉及的不同生物学过程和途径。最后，我们确定了可能逆转每种肾小球肾炎表型的新型药物和小分子化合物，表明它们应作为原发性肾小球疾病的精准治疗方法进一步进行测试。
