Asset Details
Do you wish to reserve the book?
Macrophage iron dyshomeostasis promotes aging‐related renal fibrosis
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Macrophage iron dyshomeostasis promotes aging‐related renal fibrosis
Do you wish to request the book?
Macrophage iron dyshomeostasis promotes aging‐related renal fibrosis
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Macrophage iron dyshomeostasis promotes aging‐related renal fibrosis
2024
Overview
Renal aging, marked by the accumulation of senescent cells and chronic low‐grade inflammation, leads to renal interstitial fibrosis and impaired function. In this study, we investigate the role of macrophages, a key regulator of inflammation, in renal aging by analyzing kidney single‐cell RNA sequencing data of C57BL/6J mice from 8 weeks to 24 months. Our findings elucidate the dynamic changes in the proportion of kidney cell types during renal aging and reveal that increased macrophage infiltration contributes to chronic low‐grade inflammation, with these macrophages exhibiting senescence and activation of ferroptosis signaling. CellChat analysis indicates enhanced communications between macrophages and tubular cells during aging. Suppressing ferroptosis alleviates macrophage‐mediated tubular partial epithelial‐mesenchymal transition in vitro, thereby mitigating the expression of fibrosis‐related genes. Using SCENIC analysis, we infer Stat1 as a key age‐related transcription factor promoting iron dyshomeostasis and ferroptosis in macrophages by regulating the expression of Pcbp1, an iron chaperone protein that inhibits ferroptosis. Furthermore, through virtual screening and molecular docking from a library of anti‐aging compounds, we construct a docking model targeting Pcbp1, which indicates that the natural small molecule compound Rutin can suppress macrophage senescence and ferroptosis by preserving Pcbp1. In summary, our study underscores the crucial role of macrophage iron dyshomeostasis and ferroptosis in renal aging. Our results also suggest Pcbp1 as an intervention target in aging‐related renal fibrosis and highlight Rutin as a potential therapeutic agent in mitigating age‐related renal chronic low‐grade inflammation and fibrosis.
During renal aging, the accumulation of senescent macrophages promotes tubular partial epithelial‐mesenchymal transition through the secretion of the senescence‐associated secretory phenotype, ultimately contributing to age‐related renal fibrosis. We propose that Pcbp1 is a key factor for iron homeostasis, and its downregulation promotes renal macrophage senescence by inducing iron dyshomeostasis. While the transcription factor Stat1 contributes to Pcbp1 downregulation, Rutin can preserve the level of Pcbp1 under senescent conditions. This suggests that Rutin is a promising agent for modulating the function of Pcbp1 during renal aging.
