Related Experiment Video
Updated: Jan 19, 2026
Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
BMP1 inhibitor UK383,367 attenuates renal fibrosis and inflammation in CKD
Mi Bai1,2,3, Juan Lei1,2, Shuqin Wang1,2
1Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing, China.
Abstract:
Renal fibrosis is a key pathological phenomenon of chronic kidney disease (CKD) contributing to the progressive loss of renal function. UK383,367 is a procollagen C proteinase inhibitor that has been selected as a candidate for dermal antiscarring agents, whereas its role in renal fibrosis is unclear. In the present study, UK383,367 was applied to a CKD mouse model of unilateral ureteral obstruction (UUO) and cell lines of renal tubular epithelial cells (mouse proximal tubular cells) and renal fibroblast cells (NRK-49F cells) challenged by transforming growth factor-β1. In vivo, bone morphogenetic protein 1, the target of UK383,367, was significantly enhanced in UUO mouse kidneys and renal biopsies from patients with CKD. Strikingly, UK383,367 administration ameliorated tubulointerstitial fibrosis as shown by Masson's trichrome staining in line with the blocked expression of collagen type I/III, fibronectin, and α-smooth muscle actin in the kidneys from UUO mice. Similarly, the enhanced inflammatory factors in obstructed kidneys were also blunted. In vitro, UK383,367 pretreatment inhibited the induction of collagen type I/III, fibronectin, and α-smooth muscle actin in both mouse proximal tubular cells and NRK-49F cells treated with transforming growth factor-β1. Taken together, these findings indicate that the bone morphogenetic protein 1 inhibitor UK383,367 could serve as a potential drug in antagonizing CKD renal fibrosis by acting on the maturation and deposition of collagen and the subsequent profibrotic response and inflammation.
Insights
UK383,367, a procollagen C proteinase inhibitor, effectively reduced kidney fibrosis in a mouse model of chronic kidney disease (CKD). This compound targets bone morphogenetic protein 1, mitigating collagen deposition and inflammation associated with renal fibrosis.
Area of Science:
- Nephrology
- Biochemistry
- Pharmacology
Background:
- Renal fibrosis is a critical factor in chronic kidney disease (CKD) progression and loss of kidney function.
- The role of procollagen C proteinase inhibitors, like UK383,367, in renal fibrosis is not well understood.
- Bone morphogenetic protein 1 (BMP-1) is implicated in extracellular matrix remodeling and fibrosis.
Purpose of the Study:
- To investigate the therapeutic potential of UK383,367, a BMP-1 inhibitor, in ameliorating renal fibrosis.
- To explore the effects of UK383,367 on collagen deposition and inflammatory responses in a preclinical model of CKD.
Main Methods:
- Utilized a unilateral ureteral obstruction (UUO) mouse model to induce kidney fibrosis.
- Treated mouse proximal tubular cells and NRK-49F fibroblast cells with transforming growth factor-β1 (TGF-β1) to mimic fibrotic conditions in vitro.
- Administered UK383,367 in vivo and in vitro to assess its impact on fibrotic markers and inflammation.
- Quantified collagen type I/III, fibronectin, and α-smooth muscle actin expression via Masson's trichrome staining and other methods.
Main Results:
- Bone morphogenetic protein 1 (BMP-1) expression was significantly elevated in UUO mouse kidneys and human CKD patient biopsies.
- UK383,367 treatment markedly reduced tubulointerstitial fibrosis in UUO mice, evidenced by decreased collagen and fibronectin deposition.
- The inhibitor also blunted the expression of inflammatory factors in obstructed kidneys.
- In vitro, UK383,367 inhibited TGF-β1-induced collagen and fibronectin expression in renal tubular and fibroblast cells.
Conclusions:
- UK383,367 effectively ameliorates renal fibrosis in a preclinical CKD model by inhibiting BMP-1 activity.
- The compound reduces collagen maturation and deposition, key contributors to profibrotic responses and inflammation.
- UK383,367 demonstrates potential as a therapeutic agent for managing kidney fibrosis in CKD patients.
Related Concept Videos
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:25Antihypertensive Drugs: Direct Renin Inhibitors
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
01:28Chronic Kidney Disease III: Interprofessional Care
01:30Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors