---
title: "20-HETE–GPR75 Signaling Loss Impairs Renal Hemodynamics and Promotes SA-AKI in Sepsis"
id: "biorxiv-10-loss-of-20-hete-gpr75-signaling-impairs-renal-hemodynamic-adaptation-in-sepsis"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-10-loss-of-20-hete-gpr75-signaling-impairs-renal-hemodynamic-adaptation-in-sepsis"
content_type: "clinical_feed_article"
specialty: "Nephrology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.14.751621v1?rss=1"
published_at: "2026-09-21T11:56:41.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# 20-HETE–GPR75 Signaling Loss Impairs Renal Hemodynamics and Promotes SA-AKI in Sepsis
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-10-loss-of-20-hete-gpr75-signaling-impairs-renal-hemodynamic-adaptation-in-sepsis
- **Specialty:** [Nephrology](https://medichelpline.com/clinical-feed/nephrology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.14.751621v1?rss=1)
- **Published At:** 2026-09-21T11:56:41.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- This preprint reports that sepsis reduces circulating and renal levels of **20-HETE** and lowers renal expression of the receptor **GPR75**, changes that accompany progressive renal dysfunction and tubular injury in a rat cecal ligation and puncture (CLP) model. - CLP rats showed a biphasic cardiovascular response: an early compensated phase followed by late decompensation with worsening renal function; these phases correlated with depletion of 20-HETE and reduced GPR75 signaling in kidney tissue. - Administration of a pharmacological **20-HETE** analog restored systemic and renal hemodynamics in septic rats, increased mean arterial pressure, lowered serum creatinine and blood urea nitrogen, and improved renal histology. - The renoprotective effects of the 20-HETE analog were partially reversed by inhibition of **PKC**, implicating a **PLC/PKC**-dependent signaling mechanism downstream of GPR75. - In a clinical component, circulating **20-HETE** concentrations were lower in patients with sepsis than in healthy controls and were lowest in patients with sepsis-associated acute kidney injury (**SA-AKI**); these reductions paralleled altered renal hemodynamic parameters measured by **point-of-care ultrasound**. - The study links sepsis-associated depletion of 20-HETE and impaired **GPR75** signaling with disturbed systemic and renal hemodynamics and the development of SA-AKI, and suggests that restoring 20-HETE signaling may ameliorate hemodynamic dysfunction and renal injury. - The article is a preprint and has not undergone peer review; methodological specifics such as exact dosing, sample sizes, and statistical details were reported in the source but are not restated here beyond the described outcomes.
## Clinical Analysis & Structured Key Points
Loss of 20-HETE-GPR75 Signaling Impairs Renal Hemodynamic Adaptation in Sepsis | bioRxiv Skip to main content New Results Loss of 20-HETE-GPR75 Signaling Impairs Renal Hemodynamic Adaptation in Sepsis Yaqi Han , Huaxing Zhang , Leying Li , Lixia Liu , Yanling Yin , Yuhong Chen , Xin Lin , Ruike Yang , Congcong Zhao , View ORCID Profile Zhenjie Hu doi: https://doi.org/10.64898/2026.09.14.751621 Yaqi Han 1 The Fourth Hospital of Hebei Medical University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Huaxing Zhang 2 Hebei Medical University Find this author on Google Scholar Find this author on PubMed Search for this author on this site Leying Li 1 The Fourth Hospital of Hebei Medical University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Lixia Liu 1 The Fourth Hospital of Hebei Medical University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Yanling Yin 1 The Fourth Hospital of Hebei Medical University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Yuhong Chen 1 The Fourth Hospital of Hebei Medical University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Xin Lin 1 The Fourth Hospital of Hebei Medical University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ruike Yang 1 The Fourth Hospital of Hebei Medical University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Congcong Zhao 1 The Fourth Hospital of Hebei Medical University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Zhenjie Hu 1 The Fourth Hospital of Hebei Medical University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Zhenjie Hu For correspondence: 46400533{at}hebmu.edu.cn Abstract Info/History Metrics Preview PDF Abstract BACKGROUD: Sepsis is a life-threatening condition characterized by a dysregulated host response to infection. It frequently precipitates sepsis-associated acute kidney injury (SA-AKI). 20-Hydroxyeicosatetraenoic acid (20-HETE), is an important regulator of vascular tone. We aim to investigate whether disruption of 20-HETE signaling contributes to septic renal dysfunction. METHODS: In the animal study, Sprague-Dawley rats underwent the cecal ligation and puncture to induce sepsis and SA-AKI. Comprehensive cardiac and renal ultrasonographic assessments were performed in all animals. Blood samples were collected for biochemical assessment of renal function and quantification of circulating 20-HETE levels. Kidney tissues were harvested for analysis of the 20-HETE–GPR75–PLC/PKC signaling pathway and histological evaluation by hematoxylin and eosin staining. In the clinical study, circulating 20-HETE levels and renal hemodynamic parameters derived from point-of-care ultrasound were evaluated in healthy individuals and patients with sepsis. Venous blood samples were collected for quantification of serum 20-HETE concentrations. RESULTS: Firstly, CLP-induced septic rats produced a biphasic hemodynamic response, with early compensation followed by late cardiovascular decompensation, accompanied by progressive renal dysfunction, tubular injury, depletion of circulating and renal 20-HETE, and reduced renal GPR75 expression. Secondly, Restoration of 20-HETE signaling with a pharmacological analog improved systemic and renal hemodynamics, increased MAP, reduced serum creatinine, blood urea nitrogen, and ameliorated renal pathological injury. These protective effects were partially attenuated by PKC inhibition, implicating PKC-dependent signaling in 20-HETE-mediated renal protection. Moreover, in septic patients, circulating 20-HETE concentrations were reduced compared with healthy individuals and were lowest among those with SA-AKI, paralleling alterations in renal hemodynamic parameters measured by point-of-care ultrasound. CONCLUSIONS: Sepsis-associated depletion of 20-HETE accompanies impaired systemic and renal hemodynamic regulation and is associated with the development of SA-AKI. Restoration of 20-HETE signaling improves hemodynamic function and attenuates renal injury, potentially involving GPR75-associated PLC/PKC signaling. KEY WORDS: sepsis-associated acute kidney injury, 20-hydroxyeicosatetraenoic acid, GPR75, renal hemodynamics, point-of-care ultrasonography Competing Interest Statement The authors have declared no competing interest. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Back to top Previous Next Posted September 21, 2026. Download PDF Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Loss of 20-HETE-GPR75 Signaling Impairs Renal Hemodynamic Adaptation in Sepsis Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Loss of 20-HETE-GPR75 Signaling Impairs Renal Hemodynamic Adaptation in Sepsis Yaqi Han , Huaxing Zhang , Leying Li , Lixia Liu , Yanling Yin , Yuhong Chen , Xin Lin , Ruike Yang , Congcong Zhao , Zhenjie Hu bioRxiv 2026.09.14.751621; doi: https://doi.org/10.64898/2026.09.14.751621 Share This Article: Copy Citation Tools Loss of 20-HETE-GPR75 Signaling Impairs Renal Hemodynamic Adaptation in Sepsis Yaqi Han , Huaxing Zhang , Leying Li , Lixia Liu , Yanling Yin , Yuhong Chen , Xin Lin , Ruike Yang , Congcong Zhao , Zhenjie Hu bioRxiv 2026.09.14.751621; doi: https://doi.org/10.64898/2026.09.14.751621 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (8013) Biochemistry (18743) Bioengineering (14890) Bioinformatics (44438) Biophysics (22604) Cancer Biology (19727) Cell Biology (26904) Clinical Trials (138) Developmental Biology (13966) Ecology (21006) Epidemiology (2067) Evolutionary Biology (25457) Genetics (16167) Genomics (23510) Immunology (18712) Microbiology (42520) Molecular Biology (18062) Neuroscience (93467) Paleontology (700) Pathology (2979) Pharmacology and Toxicology (5097) Physiology (8114) Plant Biology (16000) Scientific Communication and Education (2095) Synthetic Biology (4560) Systems Biology (10235) Zoology (2391)
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