The autophagy protein, ATG14 safeguards against unscheduled pyroptosis activation to enable embryo transport during early pregnancy DOI Open Access

Pooja Popli,

Arin K. Oestreich, Vineet K. Maurya

et al.

Published: Nov. 28, 2024

Recurrent pregnancy loss (RPL), characterized by two or more failed clinical pregnancies, poses a significant challenge to reproductive health. In addition embryo quality and endometrial function, proper oviduct function is also essential for successful establishment. Therefore, structural abnormalities inflammation resulting from infection in the may impede transport of embryos endometrium, thereby increasing risk miscarriage. However, our understanding biological processes that preserve oviductal cellular structure functional integrity limited. Here, we report Atg14-dependent autophagy plays crucial role maintaining controlling inflammatory responses, supporting efficient transport. Specifically, conditional depletion autophagy-related gene, Atg14 causes severe compromising its leading abnormal retention embryos. Interestingly, selective ciliary epithelial cells did not impact female fertility, highlighting specificity ATG14 distinct cell types within oviduct. Mechanistically, triggered unscheduled pyroptosis via altering mitochondrial inappropriate impeded Finally, pharmacological activation pregnant mice phenocopied genetically induced defect caused impairment Together, found safeguards against enable uterus implantation. Of significance, these findings provide possible insights into underlying mechanism(s) early might aid developing novel prevention strategies using modulators.

Language: Английский

The Renoprotective Mechanisms of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i)—A Narrative Review DOI Open Access

Liana Iordan,

Laura Gaiță, Romulus Timar

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7057 - 7057

Published: June 27, 2024

Chronic kidney disease (CKD) is a noncommunicable condition that has become major healthcare burden across the globe, often underdiagnosed and associated with low awareness. The main cause leads to development of renal impairment diabetes mellitus and, in contrast other chronic complications such as retinopathy or neuropathy, it been suggested intensive glycemic control not sufficient preventing diabetic disease. Nevertheless, novel class antidiabetic agents, sodium-glucose cotransporter-2 inhibitors (SGLT2i), have shown multiple renoprotective properties range from metabolic hemodynamic direct effects, impact on reducing risk occurrence progression CKD. Thus, this review aims summarize current knowledge regarding mechanisms SGLT2i offer new perspective innovative antihyperglycemic drugs proven pleiotropic beneficial effects that, after decades no significant progress prevention delaying decline function, start era management patients

Language: Английский

Citations

6
The autophagy protein, ATG14 safeguards against unscheduled pyroptosis activation to enable embryo transport during early pregnancy DOI Open Access

Pooja Popli,

Arin K. Oestreich, Vineet K. Maurya

et al.

Published: March 7, 2025

Recurrent pregnancy loss (RPL), characterized by two or more failed clinical pregnancies, poses a significant challenge to reproductive health. In addition embryo quality and endometrial function, proper oviduct function is also essential for successful establishment. Therefore, structural abnormalities inflammation resulting from infection in the may impede transport of embryos endometrium, thereby increasing risk miscarriage. However, our understanding biological processes that preserve oviductal cellular structure functional integrity limited. Here, we report autophagy-related protein ATG14 plays crucial role maintaining controlling inflammatory responses, supporting efficient transport. Specifically, conditional depletion gene, Atg14 causes severe compromising its leading abnormal retention embryos. Interestingly, selective ciliary epithelial cells did not impact female fertility, highlighting specificity distinct cell types within oviduct. Mechanistically, triggered unscheduled pyroptosis via altering mitochondrial inappropriate impeded Finally, pharmacological activation pregnant mice phenocopied genetically induced defect caused impairment Together, found safeguards against enable uterus implantation. Of significance, these findings provide possible insights into underlying mechanism(s) early might aid developing novel prevention strategies using autophagy modulators.

Language: Английский

Citations

0
The autophagy protein ATG14 safeguards against unscheduled pyroptosis activation to enable embryo transport during early pregnancy DOI Creative Commons

Pooja Popli,

Arin K. Oestreich, Vineet K. Maurya

et al.

eLife, Journal Year: 2025, Volume and Issue: 13

Published: March 18, 2025

Recurrent pregnancy loss, characterized by two or more failed clinical pregnancies, poses a significant challenge to reproductive health. In addition embryo quality and endometrial function, proper oviduct function is also essential for successful establishment. Therefore, structural abnormalities inflammation resulting from infection in the may impede transport of embryos endometrium, thereby increasing risk miscarriage. However, our understanding biological processes that preserve oviductal cellular structure functional integrity limited. Here, we report autophagy-related protein ATG14 plays crucial role maintaining controlling inflammatory responses, supporting efficient transport. Specifically, conditional depletion gene Atg14 causes severe compromising its integrity, leading abnormal retention embryos. Interestingly, selective loss ciliary epithelial cells did not impact female fertility, highlighting specificity distinct cell types within oviduct. Mechanistically, triggered unscheduled pyroptosis via altering mitochondrial inappropriate impeded Finally, pharmacological activation pregnant mice phenocopied genetically induced defect caused impairment Together, found safeguards against enable uterus implantation. Of significance, these findings provide possible insights into underlying mechanism(s) early might aid developing novel prevention strategies using autophagy modulators.

Language: Английский

Citations

0
Single-nucleus RNA sequencing reveals ARHGAP28 expression of podocytes as a biomarker in human diabetic nephropathy DOI Creative Commons

Fengxia Zhang,

Xianhu Tang,

Zhimei Zeng

et al.

Open Medicine, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 1, 2025

Abstract Introduction Diabetic kidney disease (DKD) represents serious diabetes-associated complications, and podocyte loss is an important histologic sign of DKD. The cellular molecular profiles podocytes in DKD have yet to be fully elucidated. Methods This study analyzed kidney-related single-nucleus RNA-seq datasets (GSE131882, GSE121862, GSE141115) human diabetic glomeruli transcriptome profiling (GSE30122). ARHGAP28 expression was validated by western blot immunohistochemistry. Results In tissues, 154 differentially expressed genes (DEGs) were identified podocytes, which enriched biological processes related nephron development extracellular matrix–receptor interactions. Similarly, the mouse kidney, 344 DEGs found, clustering pathways associated with renal signaling mechanisms like PI3K/Akt (phosphatidylinositol-3 kinase/protein kinase B) PPAR (peroxisome proliferator-activated receptor). glomeruli, 438 identified, showing significant enrichment nephropathy. Venn analysis revealed 22 common across being notably overexpressed podocytes. nephropathy model using db/db mice showed that significantly upregulated cortex glomeruli. vitro studies a high-glucose corroborated these findings. Conclusions Collectively, this provides insight into function diagnosis indicates potential biomarker

Language: Английский

Citations

0
Bioinformatics-based analysis of autophagy-related genes and prediction of potential Chinese medicines in diabetic kidney disease DOI Creative Commons
Yufeng Xing, Zining Peng, Chaoyang Ye

et al.

Digital Chinese Medicine, Journal Year: 2025, Volume and Issue: 8(1), P. 90 - 99

Published: March 1, 2025

Language: Английский

Citations

0
Metrnl as a secreted protein: Discovery and cardiovascular research DOI

Zhu‐Wei Miao,

Jin Chen,

Can-Xin Chen

et al.

Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 263, P. 108730 - 108730

Published: Oct. 12, 2024

Language: Английский

Citations

3
O‐linked β‐N‐acetylglucosamine (O‐GlcNAc) modification: Emerging pathogenesis and a therapeutic target of diabetic nephropathy DOI Creative Commons

Bingxue Qi,

Yang Chen,

Siyang Chai

et al.

Diabetic Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 16, 2024

Abstract Aims O‐Linked β‐N‐acetylglucosamine (O‐GlcNAc) modification, a unique post‐translational modification of proteins, is elevated in diabetic nephropathy. This review aims to summarize the current knowledge on mechanisms by which O‐GlcNAcylation proteins contributes pathogenesis and progression nephropathy, as well therapeutic potential targeting O‐GlcNAc for its treatment. Methods Current evidence literature was reviewed synthesized narrative review. Results Hyperglycemia increases glucose flux into hexosamine biosynthesis pathway, activates glucosamino‐fructose aminotransferase expression activity, leading production substrate UDP‐GlcNAc an increase protein kidney cells. Protein regulates function cells including mesangial cells, podocytes, proximal tubular promotes renal interstitial fibrosis, resulting damage. treatments such sodium‐glucose cotransporter 2 (SGLT‐2) inhibitors renin–angiotensin–aldosterone system (RAAS) inhibitors, delay disease progression, suppress O‐GlcNAcylation. Conclusions Increased mediates cell damage Although full significance inhibition not yet understood, it may represent novel target treating

Language: Английский

Citations

2
Chinese herbal medicine for the treatment of diabetic nephropathy: From clinical evidence to potential mechanisms DOI
Xiaoxiao Gong, Linhai Cao, Hongxia Ni

et al.

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 330, P. 118179 - 118179

Published: April 16, 2024

Language: Английский

Citations

1
DNA damage-induced AIM2 pyroptosis in high glucose-induced proximal tubular epithelial cell DOI Creative Commons
Liantao Li, Li Zhang,

Yating Cai

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Nov. 26, 2024

Pyroptosis is one of the ways to cause proximal tubular epithelial cell death in diabetic nephropathy (DN), but exact mechanism remains unclear. Absent melanoma 2 (AIM2), a sensor for double-stranded DNA, creates an inflammasome that triggers cleavage gasdermin D (GSDMD), leading type inflammatory called pyroptosis. This study investigated role AIM2 pyroptosis within cells DN. We observed significantly elevated expression renal tubules from DN patients and db/db mice, as well high glucose (HG)-induced Human Kidney-2 (HK2) cells. Besides, increased was accompanied by activation pathway (cleaved-caspase-1, GSDMD-FL, GSDMD-NT) cortex mice HG-induced HK2

Language: Английский

Citations

1
The autophagy protein, ATG14 safeguards against unscheduled pyroptosis activation to enable embryo transport during early pregnancy DOI Open Access

Pooja Popli,

Arin K. Oestreich, Vineet K. Maurya

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 21, 2024

Recurrent pregnancy loss (RPL), characterized by two or more failed clinical pregnancies, poses a significant challenge to reproductive health. In addition embryo quality and endometrial function, proper oviduct function is also essential for successful establishment. Therefore, structural abnormalities inflammation resulting from infection in the may impede transport of embryos endometrium, thereby increasing risk miscarriage. However, our understanding biological processes that preserve oviductal cellular structure functional integrity limited. Here, we report autophagy-related protein ATG14 plays crucial role maintaining controlling inflammatory responses, supporting efficient transport. Specifically, conditional depletion gene, Atg14 causes severe compromising its leading abnormal retention embryos. Interestingly, selective ciliary epithelial cells did not impact female fertility, highlighting specificity distinct cell types within oviduct. Mechanistically, triggered unscheduled pyroptosis via altering mitochondrial inappropriate impeded Finally, pharmacological activation pregnant mice phenocopied genetically induced defect caused impairment Together, found safeguards against enable uterus implantation. Of significance, these findings provide possible insights into underlying mechanism(s) early might aid developing novel prevention strategies using autophagy modulators.

Language: Английский

Citations

0