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Kidney protective effect of fermented celery polysaccharides and Eubacterium rectale in diabetic rats

ABSTRACT:

This study aimed to investigate the protective effects of non-fermented celery polysaccharides (NFCP), fermented celery polysaccharides (FCP), Eubacterium rectale (ER), and their combined intervention (ER+FCP) on Type 2 diabetes (T2D)-related kidney injury in a rat model, using untargeted urinary metabolomics and kidney function indices. We employed ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC–QTOF/MS) to analyze urinary metabolite profiles. Principal component analysis (PCA) demonstrated significant metabolic disturbances in the diabetic group (DM), while all intervention groups showed a shift towards a healthier metabolic profile, with ER and ER+FCP exhibiting the most pronounced improvements. Metabolic alterations in the intervention groups were further validated by differential metabolite analysis, with FCP inducing a larger number of significant changes compared to NFCP. The combined intervention (ER+FCP) showed synergistic effects, enhancing lipid metabolism, inflammation resolution, and the regulation of bile acids, all contributing to kidney protection. Inflammatory markers, oxidative stress, and histological analysis confirmed the efficacy of these interventions in mitigating kidney injury. Our findings highlight the potential of fermented celery polysaccharides and ER to provide enhanced protection against diabetic kidney disease through metabolic modulation and synergistic interactions.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse-phase, Liquid Chromatography MS - positive - reverse-phase

PROVIDER: MTBLS13958 | MetaboLights | 2026-03-02

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS13958_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS13958_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS13958_LC-MS_negative_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular
	m_MTBLS13958_LC-MS_positive_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular

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Project description:Background: Testican-2 is a podocyte-derived glycoprotein encoded by SPOCK2. Circulating levels of testican-2 are associated with less glomerulosclerosis and better kidney prognosis, but its biological function in the podocyte is unknown. Methods: We studied the protective effect of testican-2 on immortalized cultured human podocytes and in mice treated with adriamycin. We used immunoprecipitation-mass spectrometry to identify binding partners of testican-2 and Bio-Layer Interferometry to characterize these protein-protein interactions. Using global Spock2 knockout mice, we assessed the impact of testican-2 deficiency in models of podocyte injury and also tested whether exogenous testican-2 confers podocyte protection in these testican-2 deficient mice. Finally, we analyzed testican-2 expression in human kidney biopsy samples. Results: Testican-2 reduced reduces adriamycin-induced podocyte injury in cultured human podocytes and mice. Vitronectin is a strong binding partner for testican-2, and testican-2 inhibited inhibits the interaction between vitronectin and integrin αVβ3, an important effector of podocyte injury. Consistent with this, testican-2 administration reduced reduces activation of integrin β3 in injured podocytes. Further, Spock2 deficiency increased increases susceptibility to podocyte injury due to adriamcyin and streptozotocin induced diabetes, as determined by albuminuria, foot process effacement, nephrin expression and WT1-positive podocyte number. Importantly, exogenous testican-2 circulated circulates to the kidney, bound binds to vitronectin, reduced reduces vitronectin-integrin β3 interaction, and reduced reduces podocyte injury in Spock2 deficient mice. Finally, glomerular testican-2 expression was is reduced in human focal segmental glomerulosclerosis and diabetic kidney disease, but not tubulointerstitial nephropathy. Conclusions: These findings identify a potential mechanism for testican-2 mediated kidney protection and highlight an opportunity to therapeutically target the podocyte’s interaction with its extracellular matrix.

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Kidney protective effect of fermented celery polysaccharides and Eubacterium rectale in diabetic rats

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