The following is a summary of “Inhibition of the lncRNA 585189 prevents podocyte injury and mitochondria dysfunction by promoting hnRNP A1 and SIRT1 in diabetic nephropathy,” published in the December 2023 issue of Endocrinology by Chen, et al.
One important bad thing about diabetic nephropathy (DN) is that podocyte failure has been found. However, the researchers need to fully understand how long non-coding RNAs (lncRNAs) control this process. For a study, researchers looked at kidney tissues using unbiased RNA-sequencing (RNA-seq) and found that people with DN have a significantly higher level of ENST00000585189.1 (lncRNA 585189). Also, lncRNA 585189 was positively linked to kidney failure and increased in both DN patients and human podocytes exposed to high glucose levels.
Gain- and loss-of-function tests showed that blocking lncRNA 585189 lowered the production of ROS, fixed mitochondrial shape and membrane potential problems, and fixed damage to podocytes caused by high glucose. Using genomics, lncRNA 585189 and hnRNP A1 were expected to interact. RIP, pull-down, and EMSA tests later proved this. Additional research showed that lncRNA 585189 makes the hnRNP A1 protein less stable, which lowers its expression.
On the other hand, hnRNP A1 increased the production of lncRNA 585189. Also, both the RIP and pull-down tests showed that hnRNP A1 and SIRT1 directly interacted with each other, which made SIRT1 mRNA more stable. Their results showed that lncRNA 585189 blocks SIRT1 through hnRNP A1, which makes it harder for cells to heal from problems with mitochondria and podocytes. Focusing on lncRNA 585189 seemed a good way to fix mitochondrial failure and treat DN.
Source: sciencedirect.com/science/article/abs/pii/S0303720723002162
