Glomerular Transcriptome from Experimental Nephrotic Syndrome Model and Treatment with PPARgamma Agonists

Nephropathy was induced with puromycin amino-nucleoside (PAN) in Wistar rats and treated with daily treatments of Pioglitazone (Pio) and GQ-16. Total glomerular RNA was isolated, and mRNA libraries were generated and subjected to sequencing using NovaSeq6000 SP. Injury with PAN resulted in 1089 DEGs compared to controls, and 26 of these DEGs were restored by both Pio and GQ-16 treatments, whereas 106 unique GQ-16 regulated DEGs and 17 unique Pio-regulated DEGs were identified (Fig. 4A). Overall, Pio and GQ-16 treatment resulted in 75 and 173 DEGs compared to PAN injury, which included 29 common and 190 distinct genes (Fig. 4A). Of the 29 common DEGs, 28 DEGs were down-regulated by both Pio and GQ-16 and only 1 DEG upregulated by both treatments, when compared to PAN (Fig. 4B). Of the 190 distinct DEGs identified between Pio and GQ-16 treatments, 41 were down-regulated and 5 up-regulated by Pio and 124 down-regulated and 20 up-regulated by GQ-16 treatment.本研究采用嘌呤霉素氨基核苷（puromycin amino-nucleoside，PAN）诱导Wistar大鼠构建肾病模型，并每日给予吡格列酮（Pioglitazone，Pio）与GQ-16进行干预。随后提取大鼠肾小球总RNA，构建mRNA文库并通过NovaSeq6000 SP平台完成测序。与对照组相比，PAN造模组共筛选得到1089个差异表达基因（Differentially Expressed Genes，DEGs）；其中26个DEGs可被Pio与GQ-16共同逆转恢复，另鉴定得到106个GQ-16特异性调控的DEGs与17个Pio特异性调控的DEGs（图4A）。相较于PAN造模组，Pio与GQ-16干预组分别获得75个和173个DEGs，其中包含29个共有DEGs与190个特异性差异基因（图4A）。在上述29个共有DEGs中，28个可被Pio与GQ-16共同下调，仅1个DEG可被两种药物共同上调（相较于PAN造模组，图4B）。在Pio与GQ-16干预组间的190个特异性DEGs中，Pio可下调其中41个、上调5个；GQ-16则可下调124个、上调20个。