Related Experiment Video
Updated: May 11, 2026
14:05
A Murine Model of Irreversible and Reversible Unilateral Ureteric Obstruction
Published on: December 20, 2014
Modification of kidney barrier function by the urokinase receptor
Changli Wei1, Clemens C Möller, Mehmet M Altintas
1Nephrology Division and Program in Glomerular Disease, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA.
Nature Medicine
|December 18, 2007
Summary
Urokinase receptor (uPAR) signaling in kidney podocytes drives foot process effacement and proteinuria. Blocking alphavbeta3 integrin reduces podocyte motility and lowers urinary protein loss in mice.
Area of Science:
- Nephrology
- Cellular Biology
- Molecular Medicine
Background:
- Podocyte dysfunction, characterized by foot process effacement and proteinuria, initiates progressive kidney disease.
- Current therapies do not target the cellular mechanisms underlying podocyte dysfunction.
Purpose of the Study:
- To investigate the role of urokinase receptor (uPAR) signaling in podocyte function and kidney permeability.
- To elucidate the molecular mechanisms linking uPAR to podocyte injury and proteinuria.
Main Methods:
- Utilized genetically modified mice lacking uPAR (Plaur-/-) and studied lipopolysaccharide (LPS)-induced proteinuria.
- Employed gene transfer techniques to modulate uPAR expression in podocytes and endothelial cells.
- Investigated the activation of alphavbeta3 integrin and small GTPases (Cdc42, Rac1) in podocytes.
- Assessed podocyte motility in vitro and proteinuria levels in vivo.
Main Results:
- Podocyte uPAR signaling induces foot process effacement and proteinuria through lipid-dependent alphavbeta3 integrin activation.
- Mice lacking uPAR were protected from LPS-mediated proteinuria.
- uPAR expression in podocytes, but not endothelial cells, is essential for LPS-induced proteinuria.
- uPAR activation of alphavbeta3 integrin promotes podocyte motility and GTPase activation.
- Inhibition of alphavbeta3 integrin reduced podocyte motility and proteinuria.
Conclusions:
- uPAR signaling in podocytes plays a critical role in regulating kidney permeability and the development of proteinuria.
- Targeting the uPAR/alphavbeta3 integrin pathway represents a potential therapeutic strategy for proteinuric kidney diseases.
Related Concept Videos
01:15Drug Elimination by Renal Route: Tubular Secretion
Once the process of glomerular filtration is completed, blood carrying unfiltered drug molecules traverses through efferent arterioles and makes its way into the peritubular capillaries in the proximal tubule. A variety of carriers play a pivotal role in actively secreting drugs from these peritubular capillaries into the tubular fluid. The organic anion transporter transfers acidic drugs, against an electrochemical gradient, from the peritubular capillaries into the renal tubule cells and...
01:20Renal Corpuscle
The glomerulus and Bowman's capsule are two essential components of the nephron, which is the functional unit of the kidney. These microscopic structures play a critical role in the process of blood filtration to produce urine.
Glomerulus: Structure and Function
The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous capillaries...
Glomerulus: Structure and Function
The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous capillaries...
01:26Kidney Transplant II: Surgical Procedure
Preoperative ManagementThe primary goals of preoperative management in kidney transplantation are to optimize the patient’s metabolic state and prepare them for surgery through diet adjustments, necessary dialysis, and tailored medical treatment. This phase also involves comprehensive infection screening and patient education about the surgical procedure and postoperative care to improve outcomes and adherence.Medical ManagementA comprehensive evaluation is required for both the living donor...
01:22Acute Kidney Injury I: Introduction
Introduction:Acute Kidney Injury (AKI) describes a swift decrease in kidney function occurring over hours to days, characterized by the kidneys' failure to remove waste products from the bloodstream. This leads to dangerous complications like metabolic acidosis, fluid overload, and electrolyte imbalances, such as hyperkalemia, which can cause life-threatening arrhythmias. AKI is common in both hospital and outpatient settings, often triggered by dehydration, sepsis, or exposure to nephrotoxic...
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...
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
Accurate diagnosis and effective prevention are critical in managing Acute Kidney Injury (AKI), which is linked to high mortality rates ranging from 10% to 80%. Timely recognition of at-risk patients and careful monitoring can significantly reduce the likelihood of kidney damage.Diagnostic Assessments:The diagnostic process starts with a comprehensive medical history to identify prerenal, intrarenal, and postrenal causes.Prerenal causes, such as dehydration, hypotension, or blood loss, should...