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https://doi.org/10.1016/j.jlr.2023.100416
Title: | Mfsd2a-mediated lysolipid transport is important for renal recovery after acute kidney injury | Authors: | Loke, Randy YJ Chin, Cheen Fei Liang, Gao Wong, Bernice H Galam, Dwight LA Tan, Bryan C Chua, Geok-Lin Minegishi, Shintaro Morisawa, Norihiko Sidorov, Iulia Heijs, Bram Titze, Jens Wenk, Markus R Torta, Federico Silver, David L |
Keywords: | Science & Technology Life Sciences & Biomedicine Biochemistry & Molecular Biology Acute kidney injury Phospholipid Transporter Mfsd2a omega-3 fatty acid DHA RAT PROXIMAL TUBULE BRUSH-BORDER MFSD2A PATHOPHYSIOLOGY CHOLESTEROL DIVERSITY FLUIDITY LIPIDS BRAIN MOUSE |
Issue Date: | Aug-2023 | Publisher: | ELSEVIER | Citation: | Loke, Randy YJ, Chin, Cheen Fei, Liang, Gao, Wong, Bernice H, Galam, Dwight LA, Tan, Bryan C, Chua, Geok-Lin, Minegishi, Shintaro, Morisawa, Norihiko, Sidorov, Iulia, Heijs, Bram, Titze, Jens, Wenk, Markus R, Torta, Federico, Silver, David L (2023-08). Mfsd2a-mediated lysolipid transport is important for renal recovery after acute kidney injury. JOURNAL OF LIPID RESEARCH 64 (8). ScholarBank@NUS Repository. https://doi.org/10.1016/j.jlr.2023.100416 | Abstract: | Acute kidney injury (AKI) is a global public health concern with high mortality and morbidity. In ischemic–reperfusion injury (IRI), a main cause of AKI, the brush border membrane of S3 proximal tubules (PT) is lost to the tubular lumen. How injured tubules reconstitute lost membrane lipids during renal recovery is not known. Here, we identified Mfsd2a, a sodium-dependent lysophosphatidylcholine (LPC) transporter, to be expressed specifically in the basolateral membrane of S3 PT. Using an in vivo activity probe for Mfsd2a, transport activity was found to be specific to the S3 PT. Mice with haploinsufficiency of Mfsd2a exhibited delayed recovery of renal function after acute IRI, with depressed urine osmolality and elevated levels of histological markers of damage, fibrosis, and inflammation, findings corroborated by transcriptomic analysis. Lipidomics revealed a deficiency in docosahexaenoic acid (DHA) containing phospholipids in Mfsd2a haploinsufficiency. Treatment of Mfsd2a haploinsufficient mice with LPC-DHA improved renal function and reduced markers of injury, fibrosis, and inflammation. Additionally, LPC-DHA treatment restored S3 brush border membrane architecture and normalized DHA-containing phospholipid content. These findings indicate that Mfsd2a-mediated transport of LPC-DHA is limiting for renal recovery after AKI and suggest that LPC-DHA could be a promising dietary supplement for improving recovery following AKI. | Source Title: | JOURNAL OF LIPID RESEARCH | URI: | https://scholarbank.nus.edu.sg/handle/10635/247588 | ISSN: | 0022-2275 1539-7262 |
DOI: | 10.1016/j.jlr.2023.100416 |
Appears in Collections: | Staff Publications Elements |
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