Gessel Megan M, Spraggins Jeffrey M, Voziyan Paul A, Abrahamson Dale R, Caprioli Richard M, Hudson Billy G
Division of Nephrology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37232, USA.
Lipids. 2019 Jun;54(6-7):411-418. doi: 10.1002/lipd.12171. Epub 2019 Jun 13.
Alport syndrome is caused by mutations in collagen IV that alter the morphology of renal glomerular basement membrane. Mutations result in proteinuria, tubulointerstitial fibrosis, and renal failure but the pathogenic mechanisms are not fully understood. Using imaging mass spectrometry, we aimed to determine whether the spatial and/or temporal patterns of renal lipids are perturbed during the development of Alport syndrome in the mouse model. Our results show that most sulfatides are present at similar levels in both the wild-type (WT) and the Alport kidneys, with the exception of two specific sulfatide species, SulfoHex-Cer(d18:2/24:0) and SulfoHex-Cer(d18:2/16:0). In the Alport but not in WT kidneys, the levels of these species mirror the previously described abnormal laminin expression in Alport syndrome. The presence of these sulfatides in renal tubules but not in glomeruli suggests that this specific aberrant lipid pattern may be related to the development of tubulointerstitial fibrosis in Alport disease.
奥尔波特综合征是由IV型胶原蛋白的突变引起的，这些突变会改变肾小球基底膜的形态。突变会导致蛋白尿、肾小管间质纤维化和肾衰竭，但其致病机制尚未完全明确。我们利用成像质谱技术，旨在确定在小鼠模型中奥尔波特综合征发展过程中肾脏脂质的空间和/或时间模式是否受到干扰。我们的结果表明，除了两种特定的硫脂种类，即硫酸己糖神经酰胺（d18:2/24:0）和硫酸己糖神经酰胺（d18:2/16:0）外，大多数硫脂在野生型（WT）和奥尔波特综合征小鼠的肾脏中含量相似。在奥尔波特综合征小鼠的肾脏中，而不是野生型小鼠的肾脏中，这些硫脂的含量反映了先前描述的奥尔波特综合征中异常的层粘连蛋白表达。这些硫脂存在于肾小管而非肾小球中，这表明这种特定的异常脂质模式可能与奥尔波特病中肾小管间质纤维化的发展有关。
