Growth hormone-releasing peptide 6 (GHRP-6) hydrogel for acute kidney injury therapy via metabolic regulation.

Preclinical study involving in vitro cell culture and in vivo mouse model of acute kidney injury

“Our study aimed to investigate whether this GHRP-6 hydrogel could enhance renal structural and functional recovery in a mouse model of AKI.”

C57BL/6 albino male mice and primary renal tubular epithelial cells (TECs)

“The IRI-AKI model was established in C57BL/6 albino male mice (8–10 weeks old) as previously described [51].”

10 mice per group for metabolomic analysis; n=3 to n=5 for other in vivo and in vitro experiments

“an untargeted metabolomic approach was employed to analyze mouse kidney tissues, including 10 healthy mice in the sham group, 10 mice in the PBS group, and 10 mice in the AKI with GHRP-6 hydrogel treatment group.”

Assessments conducted at 3, 7, and 28 days post-injury in vivo; 48 hours for in vitro cell culture

“The expression of the fibrosis-related genes Col IV, α-SMA, TGF-β, and fibronectin in renal tissues was detected by real-time qPCR on day 28 post-AKI.”

GHRP-6 hydrogel treatment reduced acute tubular necrosis scores and lowered serum creatinine and blood urea nitrogen levels compared to the PBS group

“Compared with those in the PBS group, the SCr and BUN levels were significantly lower in the GHRP-treated group, indicating that renal function was restored following hydrogel administration (Fig. 2C).”

Metabolomic analysis showed that spermidine, L-glutamine, and acetyl-CoA were highly enriched in the GHRP-6 hydrogel-treated group

“Metabolomic sequencing analysis revealed that spermidine, L-glutamine, and acetyl-CoA, which are involved in amino acid and fatty acid metabolism, were highly enriched in a mouse model of AKI treated with the GHRP-6 hydrogel.”

GHRP-6 hydrogel treatment enhanced TEC survival and reduced apoptosis by activating the mTOR-P70 pathway

“Further study revealed that GHRP-6 hydrogel treatment enhanced the survival of TECs in the ischemic microenvironment by activating the mTOR-P70 pathway.”

The intrarenal injection method is invasive, limiting clinical translation, and the precise mechanistic link between metabolic reprogramming and signaling activation requires further investigation

“First, although intrarenal injection achieves high local drug concentrations and precise tissue targeting in preclinical models, it is an inherently invasive procedure, which represents a significant limitation for clinical translation.”