Illustration of a kidney being healed by proteins, symbolizing kidney disease prevention.

Unlocking Kidney Health: How a Single Protein Could Prevent Organ Damage

Avery Sinclair in Health & Wellness November 2025 • 4 min read.

"New Research Reveals the Critical Role of PAX2 and ADAM10 in Preventing Kidney Disease"

Chronic kidney disease (CKD) is a growing global health crisis, affecting millions and leading to devastating outcomes such as end-stage renal disease. Characterized by progressive renal fibrosis, CKD involves the gradual scarring of the kidneys, leading to loss of function and, ultimately, organ failure. Understanding the underlying mechanisms driving this process is crucial for developing effective therapies.

A key process in renal fibrosis is epithelial-to-mesenchymal transition (EMT), where healthy kidney cells transform into cells that produce scar tissue. This transformation involves a series of changes, including loss of cell structure and adhesion, and increased production of extracellular matrix components that contribute to fibrosis. Identifying the factors that trigger and regulate EMT is essential for preventing and treating CKD.

Recent research has focused on the role of specific proteins in promoting EMT and renal fibrosis. Two proteins of particular interest are PAX2 and ADAM10. PAX2 is a transcription factor involved in kidney development, while ADAM10 is an enzyme that cleaves other proteins, impacting various cellular processes. Understanding how these proteins interact and contribute to EMT could unlock new strategies for combating kidney disease.

PAX2 and ADAM10: The Dynamic Duo Behind Kidney Damage

Illustration of a kidney being healed by proteins, symbolizing kidney disease prevention.

A groundbreaking study has shed light on the intricate relationship between PAX2 and ADAM10 in the context of renal fibrosis. Researchers discovered that PAX2 directly influences the expression of ADAM10 in renal tubular epithelial cells, the cells lining the kidney tubules. This interaction, it turns out, plays a significant role in driving EMT and, consequently, renal fibrosis.

The study employed a variety of techniques to unravel this connection. In vitro experiments using a rat renal tubular epithelial cell line (NRK52E) showed that increasing PAX2 levels led to a corresponding increase in ADAM10 expression. Furthermore, E-cadherin levels decreased, and α-SMA levels increased, classic hallmarks of EMT.

These findings are supported by several key pieces of evidence:

PAX2 directly binds to the ADAM10 promoter region, the area of DNA that controls ADAM10 expression.
Over-expression of PAX2 significantly activated ADAM10 transcription.
Inhibiting ADAM10 partially reversed the effects of PAX2-induced EMT.
In vivo studies in rats with unilateral ureteral obstruction (UUO), a model of kidney fibrosis, showed increased expression of both PAX2 and ADAM10 in the fibrotic kidneys.

These compelling results demonstrate that PAX2 directly upregulates ADAM10 expression, which, in turn, promotes EMT in renal tubular epithelia. This PAX2-ADAM10 axis appears to be a critical pathway in the development of renal fibrosis. Importantly, researchers also found elevated ADAM10 expression in kidney tissues from patients with chronic kidney disease, reinforcing the clinical relevance of these findings.

A New Hope for Kidney Disease Treatment

This research offers a promising new avenue for developing targeted therapies to combat renal fibrosis. By understanding the critical role of the PAX2-ADAM10 axis in driving EMT, researchers can now focus on strategies to disrupt this interaction and prevent or reverse kidney damage. This could involve developing drugs that specifically inhibit ADAM10 activity or target PAX2 expression, offering new hope for patients with chronic kidney disease.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1007/s11255-018-1956-0, Alternate LINK

Title: Pax2 May Induce Adam10 Expression In Renal Tubular Epithelial Cells And Contribute To Epithelial-To-Mesenchymal Transition

Subject: Urology

Journal: International Urology and Nephrology

Publisher: Springer Science and Business Media LLC

Authors: Ling Hou, Yue Du, Chengguang Zhao, Yubin Wu

Published: 2018-08-16

Everything You Need To Know

What is chronic kidney disease, and how does it relate to renal fibrosis and EMT (epithelial-to-mesenchymal transition)?

Chronic kidney disease (CKD) involves the progressive scarring of the kidneys, known as renal fibrosis. A key process is epithelial-to-mesenchymal transition (EMT), where healthy kidney cells transform into cells that produce scar tissue. This involves changes like loss of cell structure, adhesion, and increased production of extracellular matrix components, ultimately leading to loss of kidney function and organ failure. Research focuses on understanding and targeting the factors that trigger and regulate EMT to prevent and treat CKD.

What are PAX2 and ADAM10, and what roles do they play in kidney damage?

PAX2 is a transcription factor vital in kidney development, influencing the expression of genes involved in this process. ADAM10, on the other hand, is an enzyme that cleaves other proteins, thereby affecting various cellular processes. Their interaction is critical in the context of renal fibrosis because PAX2 directly influences the expression of ADAM10 in renal tubular epithelial cells. This interaction drives EMT, leading to renal fibrosis. Therefore, understanding their dynamic is crucial for developing strategies against kidney disease.

How did researchers demonstrate the link between PAX2 and ADAM10 in promoting EMT and renal fibrosis?

Researchers discovered that PAX2 directly binds to the ADAM10 promoter region, which is the area of DNA that controls ADAM10 expression. Over-expression of PAX2 significantly activated ADAM10 transcription. Inhibiting ADAM10 partially reversed the effects of PAX2-induced EMT. In vivo studies in rats with unilateral ureteral obstruction (UUO) showed increased expression of both PAX2 and ADAM10 in the fibrotic kidneys. Elevated ADAM10 expression was also found in kidney tissues from patients with chronic kidney disease, reinforcing the clinical relevance of these findings.

What therapeutic approaches could be developed based on the understanding of the PAX2-ADAM10 axis in kidney disease?

Targeted therapies could disrupt the PAX2-ADAM10 interaction to prevent or reverse kidney damage. This could involve developing drugs that specifically inhibit ADAM10 activity or target PAX2 expression. By preventing the up regulation of ADAM10, the epithelial-to-mesenchymal transition(EMT) can be slowed and the progression of renal fibrosis can be altered. Further understanding of other proteins and factors involved in this pathway might lead to new therapies.

Does the PAX2-ADAM10 interaction fully explain renal fibrosis, or are other factors involved?

While the research has identified the PAX2-ADAM10 axis as a key player, it doesn't fully explain the entire process of renal fibrosis. Other factors, such as various growth factors, cytokines, and inflammatory responses, also contribute to the disease. Further research is needed to identify other potential therapeutic targets and understand how they interact with the PAX2-ADAM10 axis to develop more comprehensive treatment strategies for chronic kidney disease.