FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3120372118> ?p ?o ?g. }

• W3120372118 abstract "ABSTRACT Furosemide, a widely prescribed diuretic for edema-forming states, inhibits sodium reabsorption in the thick ascending limb of the nephron. Tubular adaptation to diuretics has been observed, but the range of mechanisms along the nephron has not been fully explored. Using morphometry, we show that furosemide induces renal tubular epithelial hyperplasia selectively in distal nephron segments. By comparison, we find progressive cellular hypertrophy in proximal and distal nephron segments. We next utilize single cell RNA sequencing of vehicle- and furosemide-treated mice to define potential mechanisms of diuretic resistance. Consistent with distal tubular cell hyperplasia, we detect a net increase in DCT cell number and Birc5 , an anti-apoptotic and pro-growth gene, in a subset of DCT cells, as the most prominently up-regulated gene across the nephron. We also map a gradient of cell-specific transcriptional changes congruent with enhanced distal sodium transport. Furosemide stimulates expression of the mitogen IGF-1. Thus, we developed a mouse model of inducible deletion of renal tubular IGF-1 receptor and show reduced kidney growth and proximal, but not distal, tubular hypertrophy by furosemide. Moreover, genes that promote enhanced bioavailability of IGF-1 including Igfbp1 and Igfbp5 are significantly and differentially expressed in proximal tubular segments and correspond to IGF-1R-dependent hypertrophy. In contrast, downstream PI3-kinase signaling genes including Pdk1, Akt1, Foxo3, FKBP4, Eif2BP4 , and Spp1 are significantly and differentially expressed in distal nephron segments and correspond to IGF-1R-independent hypertrophy. These findings highlight novel mechanisms of tubular remodeling and diuretic resistance, provide a repository of transcriptional responses to a common drug, and expand the implications of long-term loop diuretic use for human disease." @default.
• W3120372118 created "2021-01-18" @default.
• W3120372118 creator A5000486822 @default.
• W3120372118 creator A5011441362 @default.
• W3120372118 creator A5011483450 @default.
• W3120372118 creator A5012758116 @default.
• W3120372118 creator A5016718995 @default.
• W3120372118 creator A5016898200 @default.
• W3120372118 creator A5018881504 @default.
• W3120372118 creator A5051559059 @default.
• W3120372118 creator A5051996204 @default.
• W3120372118 creator A5083763463 @default.
• W3120372118 date "2021-01-14" @default.
• W3120372118 modified "2023-09-28" @default.
• W3120372118 title "Proximal and Distal Nephron-specific Adaptation to Furosemide" @default.
• W3120372118 cites W1530473805 @default.
• W3120372118 cites W1531025970 @default.
• W3120372118 cites W1900487466 @default.
• W3120372118 cites W1973937315 @default.
• W3120372118 cites W1974553541 @default.
• W3120372118 cites W1977107398 @default.
• W3120372118 cites W197751408 @default.
• W3120372118 cites W1979263211 @default.
• W3120372118 cites W1983698046 @default.
• W3120372118 cites W1985425785 @default.
• W3120372118 cites W1990714965 @default.
• W3120372118 cites W2000900558 @default.
• W3120372118 cites W2002841462 @default.
• W3120372118 cites W2006121851 @default.
• W3120372118 cites W2010399667 @default.
• W3120372118 cites W2011301426 @default.
• W3120372118 cites W2012706236 @default.
• W3120372118 cites W2017644027 @default.
• W3120372118 cites W2020882360 @default.
• W3120372118 cites W2028414806 @default.
• W3120372118 cites W2030155947 @default.
• W3120372118 cites W2030916798 @default.
• W3120372118 cites W2031445690 @default.
• W3120372118 cites W2038776268 @default.
• W3120372118 cites W2040618276 @default.
• W3120372118 cites W2043152960 @default.
• W3120372118 cites W2046339602 @default.
• W3120372118 cites W2049298939 @default.
• W3120372118 cites W2049506864 @default.
• W3120372118 cites W2050475853 @default.
• W3120372118 cites W2053717292 @default.
• W3120372118 cites W2054842941 @default.
• W3120372118 cites W2057616292 @default.
• W3120372118 cites W2058993283 @default.
• W3120372118 cites W2066418605 @default.
• W3120372118 cites W2070464031 @default.
• W3120372118 cites W2073910389 @default.
• W3120372118 cites W2077951653 @default.
• W3120372118 cites W2082713658 @default.
• W3120372118 cites W2085715185 @default.
• W3120372118 cites W2087835012 @default.
• W3120372118 cites W2090099477 @default.
• W3120372118 cites W2090831099 @default.
• W3120372118 cites W2097374264 @default.
• W3120372118 cites W2104177557 @default.
• W3120372118 cites W2107665951 @default.
• W3120372118 cites W2111410841 @default.
• W3120372118 cites W2111907151 @default.
• W3120372118 cites W2112981515 @default.
• W3120372118 cites W2113055021 @default.
• W3120372118 cites W2122858554 @default.
• W3120372118 cites W2127424513 @default.
• W3120372118 cites W2130685053 @default.
• W3120372118 cites W2134296407 @default.
• W3120372118 cites W2136256418 @default.
• W3120372118 cites W2136901254 @default.
• W3120372118 cites W2138323164 @default.
• W3120372118 cites W2138585774 @default.
• W3120372118 cites W2139250630 @default.
• W3120372118 cites W2140132128 @default.
• W3120372118 cites W2144862658 @default.
• W3120372118 cites W2146936606 @default.
• W3120372118 cites W2147621031 @default.
• W3120372118 cites W2150024906 @default.
• W3120372118 cites W2155060398 @default.
• W3120372118 cites W2157753653 @default.
• W3120372118 cites W2159258864 @default.
• W3120372118 cites W2159319899 @default.
• W3120372118 cites W2164376448 @default.
• W3120372118 cites W2167895856 @default.
• W3120372118 cites W2179438025 @default.
• W3120372118 cites W2189547245 @default.
• W3120372118 cites W2248149147 @default.
• W3120372118 cites W2265256831 @default.
• W3120372118 cites W2316788154 @default.
• W3120372118 cites W2324086411 @default.
• W3120372118 cites W2483562524 @default.
• W3120372118 cites W2513613066 @default.
• W3120372118 cites W2559944576 @default.
• W3120372118 cites W2578604801 @default.
• W3120372118 cites W2592066299 @default.
• W3120372118 cites W2595380400 @default.
• W3120372118 cites W2609525567 @default.
• W3120372118 cites W2736967138 @default.
• W3120372118 cites W2783835054 @default.

• next