PMID-18061177 – KPV PepT1-Mediated Uptake Reduces Intestinal Inflammation
Dalmasso G, Charrier-Hisamuddin L, Nguyen HT, Yan Y, Sitaraman S, Merlin D. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008;134(1):166-178.
Quick Reference
| Property | Value |
|---|---|
| PMID | 18061177 |
| DOI | 10.1053/j.gastro.2007.10.026 |
| Year | 2008 |
| Journal | Gastroenterology |
| Study Type | Animal in vivo |
| Evidence Level | V |
| Sample | Murine models (DSS and TNBS colitis) |
| Peptide(s) Studied | KPV |
Key Findings
- KPV is transported into colonocytes via the intestinal peptide transporter PepT1, establishing a specific uptake mechanism for this tripeptide in the gut
- Oral administration of KPV significantly reduced colonic inflammation in both DSS-induced and TNBS-induced murine colitis models
- KPV inhibited NF-κB activation in colonocytes, providing a mechanistic explanation for its anti-inflammatory effects
- PepT1 expression is upregulated during intestinal inflammation, potentially enhancing KPV uptake at sites of active disease
- The study demonstrated that KPV retains anti-inflammatory activity when delivered orally, supporting the feasibility of oral peptide therapy for colitis
Study Design
In vivo murine colitis models using both DSS (dextran sodium sulfate) and TNBS (2,4,6-trinitrobenzenesulfonic acid) to induce acute colitis. KPV was administered orally and its uptake was assessed via PepT1 transporter function in colonocyte cultures. NF-κB activation was measured in treated and untreated cells. Histological scoring and cytokine analysis were used to assess anti-inflammatory efficacy.
Limitations
- Animal model data; no human clinical validation
- Short-term colitis models may not reflect chronic IBD pathophysiology
- Dose-response relationships in humans remain undefined
- PepT1 expression and function may differ between murine and human intestinal epithelium
Clinical Relevance
This is a cornerstone GI mechanism study for KPV. It establishes that KPV has a specific intestinal transporter (PepT1) enabling oral bioavailability in the colon, and demonstrates direct anti-inflammatory activity via NF-κB inhibition. The upregulation of PepT1 during inflammation suggests a self-amplifying therapeutic mechanism — the more inflamed the tissue, the more KPV it absorbs. This provides strong preclinical rationale for KPV in inflammatory bowel conditions and supports oral capsule formulations.
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#research #animal-in-vivo #evidence-level-V