Related Experiment Video

Updated: Jan 7, 2026

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
10:31

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice

Published on: May 2, 2025

576

JAK-STAT pathway activation compromises nephrocyte function in a Drosophila high-fat diet model of chronic kidney

Yunpo Zhao1,2, Jianli Duan1,2, Hannah Seah1,2

  • 1Center for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine, Baltimore, United States.

Elife
|December 31, 2025
PubMed

Insights

A high-fat diet damages kidney filtration cells in flies by activating the JAK-STAT pathway. Inhibiting this pathway restored kidney function, suggesting a new target for treating kidney disease.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Physiology

Background:

  • Chronic kidney disease (CKD) prevalence is increasing globally.
  • Podocyte dysfunction is a hallmark of diabetic kidney disease (DKD).
  • The JAK-STAT pathway is implicated in DKD pathogenesis.

Purpose of the Study:

  • To investigate the effects of a high-fat diet (HFD) on kidney function using a *Drosophila* model.
  • To elucidate the molecular mechanisms underlying HFD-induced nephropathy.
  • To explore the role of the JAK-STAT pathway in the adipose tissue-nephrocyte axis.

Main Methods:

  • Utilized a *Drosophila* model to study HFD-induced kidney dysfunction.
  • Examined structural and functional changes in nephrocytes.
  • Investigated the activation of the JAK-STAT pathway and the role of the adipokine Upd2.
  • Employed genetic and pharmacological inhibition of JAK-STAT signaling.

Main Results:

  • HFD disrupted the slit diaphragm structure and reduced filtration function in *Drosophila* nephrocytes.
  • HFD activated the JAK-STAT pathway in nephrocytes, mediated by increased Upd2 expression and release from the fat body.
  • Inhibition of JAK-STAT signaling ameliorated HFD-associated nephrocyte dysfunction.

Conclusions:

  • The JAK-STAT signaling pathway is crucial in the adipose tissue-nephrocyte axis and contributes to HFD-associated nephropathy.
  • Targeting the JAK-STAT pathway presents a potential therapeutic strategy for DKD and CKD.
  • This study provides novel insights into the molecular underpinnings of metabolic kidney disease.

Keywords:
D. melanogasterDrosophilaJAK-STATPydUpd2cell biologynephrocyteslit diaphragm

More Related Videos

Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease08:15

Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease

Published on: May 10, 2024

893
A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy07:52

A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy

Published on: November 7, 2017

21.8K

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
11.8K
Acute Kidney Injury II: Pathophysiology01:29

Acute Kidney Injury II: Pathophysiology

Acute kidney injury (AKI) causes are categorized into three primary categories based on the location of the injury: prerenal, intrarenal (or intrinsic), and postrenal causes. This classification guides clinical management and illustrates how different pathways can impair kidney function.Etiology and Pathophysiology of Acute Kidney Injury1. Prerenal causesEtiology: Prerenal Acute Kidney Injury, the most common type, occurs when reduced blood flow to the kidneys decreases filtration capacity...
840
Chronic Kidney Disease II: Clinical Manifestations01:24

Chronic Kidney Disease II: Clinical Manifestations

Chronic Kidney Disease (CKD) progressively impairs multiple body systems due to the accumulation of uremic toxins, which disrupt cellular functions across various organs.Neurologic symptomsNeurologic symptoms often arise early in CKD, as uremic toxin buildup drives changes in cognitive and motor functions. Patients frequently experience fatigue, headache, confusion, difficulty concentrating, and, in severe cases, seizures. Peripheral neuropathy commonly manifests as burning sensations in the...
520
Chronic Kidney Disease I: Introduction01:25

Chronic Kidney Disease I: Introduction

Chronic Kidney Disease (CKD) arises when the kidneys progressively lose their ability to function, ultimately leading to end-stage renal disease. At this advanced stage, the kidneys can no longer filter waste or maintain essential body functions, requiring renal replacement therapy (RRT) through dialysis or a kidney transplant for survival.Early-stage chronic kidney disease and detection challengesIn CKD's early stages, symptoms often remain absent because healthy nephrons compensate for...
536