Chronic kidney disease (CKD) poses a significant global health issue, leading to the progressive loss of kidney function. Renal fibrosis commonly accompanies CKD, characterized by excessive deposition of extracellular matrix (ECM). This process causes tissue remodeling and scarring in the renal parenchyma. Myofibroblasts drive renal fibrosis through their proliferation and activation.

Researchers have extensively studied Meis1 (myeloid ecotropic viral integration site 1) and its role in CKD. They focused on how Meis1 targets protein tyrosine phosphatase receptor J (Ptprj) to inhibit renal fibrosis. In CKD patients and murine models, they observed increased Meis1 expression localized in the nucleus, with levels inversely correlated to serum creatinine levels.

To explore Meis1's role in renal fibrosis further, scientists established a unilateral ureteral obstruction (UUO) model. They also used a conditional knock-in (cKI) mouse model to overexpress Meis1 specifically in fibroblasts. RNA sequencing analysis revealed that Meis1 suppresses renal fibrosis by modulating Ptprj expression.

We are excited to share a recent study published in Advanced Science by one of our clients. The scientists utilized GJ103 (sodium, MedChemExpress) and Lamin B1 Antibody (MedChemExpress) to achieve remarkable results in CKD research.

In this study, scientists used GJ103 as a potential activator of Ptprj to evaluate its protective effects against renal fibrosis. They conducted computer-aided virtual screening and in vitro experiments, discovering that GJ103 significantly inhibits the phosphorylation level of PDGFRβ. They validated this effect in NRK-49F cells stimulated with TGF-β1.

Specifically, researchers pre-treated NRK-49F cells with various concentrations of GJ103 (5, 10, 20, 40 μM) before TGF-β1 stimulation. The results showed that GJ103 markedly reduced the expression of p-PDGFRβ, especially at concentrations of 20 μM and above. Additionally, GJ103 treatment suppressed the protein expression of the fibrosis marker FN1.

To confirm the in vivo protective effects of GJ103, scientists conducted experiments using UUO and unilateral ischemia/reperfusion injury (UIRI) mouse models. In the UUO model, they pre-treated mice with GJ103 (15 mg/kg/day and 30 mg/kg/day) via intraperitoneal injection 24 hours before surgery, continuing treatment for 7 consecutive days. In the UIRI model, they administered GJ103 (30 mg/kg/day) 24 hours before surgery, continuing for 14 days.

Researchers used the Lamin B1 antibody in Western Blot assays as a control for nuclear protein extraction. They isolated nuclear and cytoplasmic proteins from kidney tissues using NE-PER Nuclear and Cytoplasmic Extraction Reagents. Then, they conducted Western Blot analysis to detect Meis1 expression in both fractions, with Lamin B1 serving as a loading control for nuclear proteins.

Histological analysis revealed that GJ103 treatment significantly alleviated renal fibrosis, as evidenced by reduced staining areas in Masson's trichrome and Picrosirius Red staining. Additionally, GJ103 treatment decreased the mRNA and protein levels of FN1, Collagen I, Collagen III, and α-SMA in the kidneys, demonstrating its significant protective effects against renal fibrosis.

The results demonstrated that Meis1 was predominantly expressed in the nucleus, which is consistent with the findings from immunofluorescence staining.

1. Expression of Meis1 is increased in the kidneys of CKD patients and mice, and negatively correlates with serum creatinine levels.

2. Overexpression of Meis1 attenuates the development of renal fibrosis, potentially through transcriptional regulation of Ptprj expression, thereby inhibiting the proliferation and activation of fibroblasts.

3. Ptprj is a transcriptional target of Meis1, and its overexpression inhibit TGF-β1-induced renal fibrosis.

4. GJ103, identified as a Ptprj activator through computer-aided virtual screening, attenuates renal fibrosis and represents a novel potential therapeutic target for the treatment of CKD.

In conclusion, this study comprehensively investigated the role of Meis1 in renal fibrosis and CKD. It found that Meis1 is upregulated in fibrotic kidneys and can inhibit fibroblast proliferation and activation by targeting Ptprj, thereby alleviating renal fibrosis. Additionally, a novel Ptprj activator, GJ103, was identified, which showed significant antifibrotic effects in vitro and in vivo. These findings suggest that the Meis1/Ptprj axis holds great therapeutic potential for treating CKD.