Related Experiment Video
Updated: May 24, 2026
04:37
Unilateral Ureteral Obstruction Model for Investigating Kidney Interstitial Fibrosis
Published on: April 25, 2025
Reduced Klotho expression level in kidney aggravates renal interstitial fibrosis
Hidekazu Sugiura1, Takumi Yoshida, Shunji Shiohira
1Dept. of Medicine IV, Tokyo Women's Medical Univ., 8-1 Kawada-cho, Shinjuku-city, Tokyo, Japan 162-8666. sugiura@kc.twmu.ac.jp
American Journal of Physiology. Renal Physiology
|February 17, 2012
Summary
Low Klotho gene expression in the kidneys worsens renal fibrosis, a key factor in chronic kidney disease (CKD). This study reveals a detrimental cycle where fibrosis further reduces Klotho, accelerating CKD progression.
Area of Science:
- Nephrology
- Molecular Biology
- Pathophysiology
Background:
- Chronic kidney disease (CKD) is characterized by renal fibrosis.
- Renal Klotho gene expression is significantly reduced in CKD.
- The relationship between Klotho and renal fibrosis is not fully understood.
Purpose of the Study:
- To investigate whether decreased Klotho expression causes or results from renal fibrosis.
- To explore the molecular mechanisms linking Klotho and renal fibrosis.
Main Methods:
- Induction of renal fibrosis using unilateral ureteral obstruction (UUO) in Klotho-deficient (kl/+) mice and wild-type littermates.
- Analysis of fibrosis markers (α-SMA, fibronectin, TGF-β(1)) in kidney tissues.
- In vitro studies using cultured renal fibroblast (NRK49F) and epithelial cells (IMCD, HRPTE) treated with recombinant Klotho protein or TGF-β(1) inhibitors.
Main Results:
- UUO kidneys in kl/+ mice exhibited significantly higher levels of fibrosis markers compared to wild-type mice.
- Recombinant Klotho protein suppressed α-SMA and PAI1 expression in renal fibroblasts, an effect mimicked by a TGF-β(1) receptor inhibitor.
- TGF-β(1) treatment reduced Klotho expression in renal epithelial cells, indicating a feedback loop.
Conclusions:
- Reduced renal Klotho expression exacerbates renal fibrosis by enhancing TGF-β(1) signaling, suggesting it is a causative factor.
- Renal fibrosis can decrease Klotho expression, creating a vicious cycle that contributes to CKD progression.
- Targeting Klotho may offer a therapeutic strategy for mitigating renal fibrosis in CKD.
Related Concept Videos
01:29Acute 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...
01:10Nephrons
The kidneys are intricate organs with millions of working units known as nephrons. Each nephron features two major structures: the renal corpuscle, which facilitates blood plasma filtration, and the renal tubule, which handles the glomerular filtrate. Blood supply is directly linked to the nephrons. The renal corpuscle consists of the glomerulus, a capillary network, and the Bowman's capsule, a double-walled epithelial structure that encases the glomerulus. The filtering of blood plasma happens...
01:25Chronic 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...
01:24Nephrotic Syndrome I : Introduction
Nephrotic Syndrome is a chronic kidney disorder defined by clinical findings such as severe proteinuria, hypoalbuminemia, hyperlipidemia, and edema. These symptoms result from damage to the glomeruli, the kidney’s filtering units, increasing their permeability to proteins.Definition and Meaning:Proteinuria, defined as the loss of more than 3.5 grams of protein per day in adults, is a crucial feature of nephrotic syndrome. This condition is often accompanied by edema, the accumulation of fluid...
01:28Chronic Kidney Disease III: Interprofessional Care
Chronic kidney disease (CKD) requires collaborative and comprehensive management. CKD progresses through stages and can lead to end-stage kidney disease (ESKD) if untreated. Interprofessional collaboration and patient education are crucial, enabling patients to manage their health and improve their quality of life.Diagnostic approach for chronic kidney diseaseThe diagnosis of CKD primarily focuses on the glomerular filtration rate (GFR), which assesses kidney function by measuring how well...
01:24Chronic 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...