Effects of Lactobacillus plantarum HFY15 on Lupus Nephritis in Mice by Regulation of the TGF-β1 Signaling Pathway

Abstract

Objective In this study, the Lactobacillus plantarum HFY15 (LP-HFY15) strain isolated from naturally fermented yak yogurt was investigated. An animal model of lupus nephritis was established by pristane to verify the interventional effect of LP-HFY15 on mouse lupus nephritis by regulating the transforming growth factor-β1 (TGF-β1) signaling pathway. Materials and Methods Indexes in mouse serum and tissues were detected by kits, pathological changes in mouse kidney were observed by hematoxylin-eosin (H&E) staining, and quantitative polymerase chain reaction (qPCR) was used to detect TGF-β 1-related expression in mouse kidney tissue, which further elucidated the mechanism of LP-HFY15. Results LP-HFY15 decreased the elevation of urinary protein and the levels of interleukin-6 (IL-6), IL-12, tumor necrosis factor alpha (TNF-α), and interferon γ (IFN-γ) in serum and kidney tissue. LP-HFY15 also reduced serum creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), and raised total protein (TP), and albumin (ALB) levels in mice with nephritis. In addition, LP-HFY15 inhibited the positive rate of double-stranded deoxyribonucleic acid (dsDNA) antibodies in mice with nephritis. The observation of H&E sections showed that LP-HFY15 alleviated the glomerulus morphological incompleteness and inflammatory infiltration caused by nephritis. Further results showed that LP-HFY15 downregulated the mRNA expression of TGF-β1, vascular endothelial growth factor (VEGF), and nuclear factor kappa-B (NF-κB) in the kidneys of lupus nephritis mice, and the expression of inhibitor of NF-κB (IκB-α), copper/zinc superoxide dismutase (Cu/Zn-SOD), and manganese superoxide dismutase (Mn-SOD) was also upregulated. Conclusion These results indicated that LP-HFY15 plays a significant role in experimental intervention for lupus nephritis. The effect of LP-HFY15 was positively correlated with its concentration, and the effect was similar to that of prednisone at 10 9 CFU/kg.

Probiotics as a complementary treatment in systemic lupus erythematosus: A systematic review

“…According to Cheng et al, intraperitoneal injection of L. plantarum at a dose of 10 9 for 12 weeks reduced kidney damage, increased copper/zinc superoxide dismutase (Cu/Zn‐SOD), and decreased inflammatory cytokines in lupus mice. In another study, L. plantarum demonstrated regulatory effects, including an increase in IL‐10 and T regulatory (Treg) 24 …”

“…In another study, L. plantarum demonstrated regulatory effects, including an increase in IL-10 and T regulatory (Treg). 24 Studies have shown that the consumption of L. casei, L. plantarum, or L. reuteri in mice has anti-inflammatory, antiapoptotic, and modulatory effects and increases the lifespan of SLE mice. [24][25][26] T A B L E 1 Effect of probiotics in in vitro studies.…”

“…24 Studies have shown that the consumption of L. casei, L. plantarum, or L. reuteri in mice has anti-inflammatory, antiapoptotic, and modulatory effects and increases the lifespan of SLE mice. [24][25][26] T A B L E 1 Effect of probiotics in in vitro studies. Kim et al demonstrated that taking L. acidophilus with tacrolimus for a duration of 8 weeks decreased dsDNA and Th17 cells while increasing Treg cells in both the spleen and peripheral blood.…”

“…These findings suggest a potential cooperative interaction among the species, enhancing the overall effectiveness by multiplying each individual strain's strength. 31 Cheng et al 24 + + ? + -+ --+ + 6…”

“…28 Khorasani et al and Mardani et al demonstrated the effectiveness of L. rhamnosus and L. delbrueckii in increasing Tregs, reducing inflammatory cytokines, and decreasing disease severity in SLEinduced mice 29,30. Other studies conducted on various types of bacteria, such as Bacteroides fragilis, 36 L. fermentum,22,23 L. reuteri,35 L. acidophilus, 27 L. paracasei, 33 L. plantarum,24 or L. casei,26 as a tolerogenic probiotic,…”