TLR4 mutant mice are protected from renal fibrosis and chronic kidney disease progression DOI Creative Commons

Ana C. P. Souza,

Takayuki Tsuji, Irina N. Baranova

и другие.

Physiological Reports, Год журнала: 2015, Номер 3(9), С. e12558 - e12558

Опубликована: Сен. 1, 2015

Chronic kidney disease (CKD) is associated with persistent low-grade inflammation and immunosuppression. In this study we tested the role of Toll-like receptor 4, main for endotoxin (LPS), in a mouse model renal fibrosis progressive CKD that better resembles human disease. C3HeJ (TLR4 mutant) mice have missense point mutation TLR4 gene, rendering nonfunctional. after folic acid injection, mutant developed less interstititial comparison to wild-type (WT) mice. Furthermore, 4 weeks 5/6 nephrectomy continuous low-dose angiotensin II infusion, C3HeOuJ WT) albuminuria, increased serum levels BUN creatinine, glomerulosclerosis, interstitial fibrosis, whereas were significantly protected from progression. WT also systemic inflammation, splenocyte apoptosis expression immune inhibitory PD-1 spleen, which not observed vitro, (LPS) directly upregulated NLRP3 inflammasome epithelial cells via TLR4. summary, contributes progression, at least part, activation cells, may participate dysregulated response CKD.

Язык: Английский

Geniposide Improves Diabetic Nephropathy by Enhancing ULK1-Mediated Autophagy and Reducing Oxidative Stress through AMPK Activation DOI Open Access
Theodomir Dusabimana, Eun‐Jung Park,

Jihyun Je

и другие.

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(4), С. 1651 - 1651

Опубликована: Фев. 6, 2021

Diabetic nephropathy (DN) is a common pathological feature in patients with diabetes and the leading cause of end-stage renal disease. Although several pharmacological agents have been developed, management DN remains challenging. Geniposide, natural compound has reported for anti-inflammatory anti-diabetic effects; however, its role poorly understood. This study investigated protective effects geniposide on underlying mechanisms. We used C57BL/6 mouse model combination high-fat diet streptozotocin after unilateral nephrectomy treated by oral gavage 5 weeks. Geniposide effectively improves DN-induced structural functional abnormalities reducing albuminuria, podocyte loss, glomerular tubular injury, inflammation interstitial fibrosis. These changes induced were associated an increase AMPK activity to enhance ULK1-mediated autophagy response decrease AKT block oxidative stress, fibrosis diabetic kidney. In addition, increased activities PKA GSK3β, possibly modulating pathways, efficiently improving dysfunction ameliorating progression DN. Conclusively, enhances reduces fibrosis, suggesting as promising treatment

Язык: Английский

Процитировано

60
What’s New in the Molecular Mechanisms of Diabetic Kidney Disease: Recent Advances DOI Open Access
Kimio Watanabe, Emiko Sato, Eikan Mishima

и другие.

International Journal of Molecular Sciences, Год журнала: 2022, Номер 24(1), С. 570 - 570

Опубликована: Дек. 29, 2022

Diabetic kidney disease (DKD) is the leading cause of chronic disease, including end-stage and increases risk cardiovascular mortality. Although treatment options for DKD, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, sodium-glucose cotransporter 2 mineralocorticoid antagonists, have advanced, their efficacy still limited. Thus, a deeper understanding molecular mechanisms DKD onset progression necessary development new innovative treatments DKD. The complex pathogenesis includes various different pathways, can be broadly classified into inflammatory, fibrotic, metabolic, hemodynamic factors. Here, we summarize recent findings in basic research, focusing on each factor advances Collective evidence from clinical research studies helpful definitive regulatory systems. Further comprehensive exploration warranted to advance our knowledge establish novel preventive strategies.

Язык: Английский

Процитировано

53
miRNA-93-5p in exosomes derived from M2 macrophages improves lipopolysaccharide-induced podocyte apoptosis by targeting Toll-like receptor 4 DOI Open Access
Zhu Wang,

Wan-sen Sun,

Ruiping Li

и другие.

Bioengineered, Год журнала: 2022, Номер 13(3), С. 7683 - 7696

Опубликована: Март 1, 2022

Diabetic nephropathy (DN) is a common complication of diabetes mellitus which can result in renal failure and severely affect public health. Several studies have revealed the important role podocyte injury DN progression. Although, involvement exosomes derived from M2 macrophages has been reported injury, underlying molecular mechanism macrophage-secreted not fully elucidated. Our study suggests that mitigate lipopolysaccharide (LPS)-induced podocytes via exosomes. Moreover, we observed miR-93-5p expression was markedly upregulated macrophages. Inhibition macrophage resulted apoptosis LPS-treated podocytes. Additionally, TLR4 showed potential to bind miR-93-5p. Subsequently, validated downstream target Further findings indicated silencing reversed renoprotective effects miR-93-5p-containing on LPS-induced injury. In summary, our demonstrated attenuated by regulating miR-93-5p/TLR4 axis, provides new perspective for treatment patients with DN.

Язык: Английский

Процитировано

40
Understanding the podocyte immune responses in proteinuric kidney diseases: from pathogenesis to therapy DOI Creative Commons
Hong Jiang,

Zhirang Shen,

Jing Zhuang

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 14

Опубликована: Янв. 15, 2024

The glomerular filtration barrier, comprising the inner layer of capillary fenestrated endothelial cells, outermost podocytes, and basement membrane between them, plays a pivotal role in kidney function. Podocytes, terminally differentiated epithelial are challenging to regenerate once injured. They essential for maintaining integrity barrier. Damage resulting from intrinsic or extrinsic factors, leads proteinuria early stages eventually progresses chronic disease (CKD). Immune-mediated podocyte injury is primary pathogenic mechanism proteinuric diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, lupus nephritis with involvement. An extensive body evidence indicates that podocytes not only contribute significantly maintenance barrier serve as targets immune responses but also exhibit cell-like characteristics, participating both innate adaptive immunity. play mediating represent potential therapeutic CKD. This review aims systematically elucidate mechanisms various lesions provide an overview recent advances immunotherapy. It offers valuable insights deeper understanding identification new targets, has significant implications future clinical diagnosis treatment podocyte-related disorders.

Язык: Английский

Процитировано

13
TLR4 mutant mice are protected from renal fibrosis and chronic kidney disease progression DOI Creative Commons

Ana C. P. Souza,

Takayuki Tsuji, Irina N. Baranova

и другие.

Physiological Reports, Год журнала: 2015, Номер 3(9), С. e12558 - e12558

Опубликована: Сен. 1, 2015

Chronic kidney disease (CKD) is associated with persistent low-grade inflammation and immunosuppression. In this study we tested the role of Toll-like receptor 4, main for endotoxin (LPS), in a mouse model renal fibrosis progressive CKD that better resembles human disease. C3HeJ (TLR4 mutant) mice have missense point mutation TLR4 gene, rendering nonfunctional. after folic acid injection, mutant developed less interstititial comparison to wild-type (WT) mice. Furthermore, 4 weeks 5/6 nephrectomy continuous low-dose angiotensin II infusion, C3HeOuJ WT) albuminuria, increased serum levels BUN creatinine, glomerulosclerosis, interstitial fibrosis, whereas were significantly protected from progression. WT also systemic inflammation, splenocyte apoptosis expression immune inhibitory PD-1 spleen, which not observed vitro, (LPS) directly upregulated NLRP3 inflammasome epithelial cells via TLR4. summary, contributes progression, at least part, activation cells, may participate dysregulated response CKD.

Язык: Английский

Процитировано

88