Evidence map›Paper›PMID 39843996›Full record

ArticleDiabetes & metabolism journal2025

Ras Guanine Nucleotide-Releasing Protein-4 Inhibits Erythropoietin Production in Diabetic Mice with Kidney Disease by Degrading HIF2A.

Junmei Wang, Shuai Huang, Li Zhang, Yixian He, Xian Shao, A-Shan-Jiang A-Ni-Wan, Yan Kong, Xuying Meng, Pei Yu, Saijun Zhou

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In one paragraph

Article in Diabetes & metabolism journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Junmei Wang *NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
Shuai Huang *NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
Li Zhang *NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
Yixian HeNHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
Xian ShaoNHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
A-Shan-Jiang A-Ni-WanNHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
Yan KongNHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
Xuying MengNHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
Pei YuNHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
Saijun ZhouNHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.

Funding

Bethune Charitable Foundation Z04JKM2022E035China Endocrine Metabolism Talent Research Fund 2022-N-02-07China Endocrine Metabolism Talent Research Fund 2023-N-03-15Hubei Chen Xiaoping Science and Technology Development Fund CXPJJH122012-002National Natural Science Foundation of China 81600643Nature Science Foundation of Tianjin, China 21JCQNJC00460Public Health Science and Technology Major Special Project 21ZXGWSY00100Tianjin Education Commission 2022KJ248Tianjin Education Commission 2024ZD036Tianjin Key Laboratory of Metabolic Diseases ZXYZDSYSZD2022-1Tianjin Key Medical Discipline (Specialty) Construction Project TJYXZDXK-032ATianjin Medical University Chu Hsien-I Memorial HospitalTianjin Science and Technology Plan Project
6 · The paper itself

Abstract

backgruoundIn acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes.

methodsThe degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments.

resultsRasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination-proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice.

conclusionRasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Indexed as

Basic Helix-Loop-Helix ProteinsDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2Diabetic NephropathiesErythropoietinGuanine Nucleotide Exchange FactorsAnimalsEndothelial PAS Domain-Containing Protein 1KidneyMaleMiceMice, Inbred C57BLBasic Helix-Loop-Helix ProteinsEndothelial PAS Domain-Containing Protein 1ErythropoietinGuanine Nucleotide Exchange FactorsDiabetes mellitus, type 2ErythropoietinInflammationRas guanine nucleotide releasing protein 4

Identifiers

PMID39843996
PMCPMC12086582

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.