Obstructive nephropathy and molecular pathophysiology of renal interstitial fibrosis DOI Creative Commons
Rikke Nørregaard, Henricus A. M. Mutsaers, Jørgen Frøkiær

et al.

Physiological Reviews, Journal Year: 2023, Volume and Issue: 103(4), P. 2847 - 2892

Published: July 13, 2023

The kidneys play a key role in maintaining total body homeostasis. complexity of this task is reflected the unique architecture organ. Ureteral obstruction greatly affects renal physiology by altering hemodynamics, changing glomerular filtration and metabolism, inducing architectural malformations kidney parenchyma, most importantly fibrosis. Persisting pathological changes lead to chronic disease, which currently ∼10% global population one major causes death worldwide. Studies on consequences ureteral date back 1800s. Even today, experimental unilateral (UUO) remains standard model for tubulointerstitial However, has certain limitations when it comes studying tubular injury repair, as well limited potential human translation. Nevertheless, provided scientific community with wealth knowledge (patho)physiology. With introduction advanced omics techniques, classical UUO remained relevant day been instrumental understanding fibrosis at molecular, genomic, cellular levels. This review details concepts recent advances obstructive nephropathy, highlighting pathophysiological hallmarks responsible functional induced obstruction, special emphasis

Language: Английский

ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis DOI
Triet M. Bui, Hannah L. Wiesolek, Ronen Sumagin

et al.

Journal of Leukocyte Biology, Journal Year: 2020, Volume and Issue: 108(3), P. 787 - 799

Published: March 17, 2020

Abstract ICAM-1 is a cell surface glycoprotein and an adhesion receptor that best known for regulating leukocyte recruitment from circulation to sites of inflammation. However, in addition vascular endothelial cells, expression also robustly induced on epithelial immune cells response inflammatory stimulation. Importantly, serves as biosensor transduce outside-in-signaling via association its cytoplasmic domain with the actin cytoskeleton following ligand engagement extracellular domain. Thus, has emerged master regulator many essential cellular functions both at onset resolution pathologic conditions. Because role driving responses well recognized, this review will mainly focus newly emerging roles injury-resolution responses, effector function inflammation tumorigenesis. been clinical therapeutic interest some time now; however, several attempts inhibiting improve injury have failed. Perhaps, better understanding beneficial or tumorigenesis spark new revisiting value potential target.

Language: Английский

Citations

669
Shared and distinct mechanisms of fibrosis DOI
Jörg H. W. Distler, Andrea‐Hermina Györfi, Meera Ramanujam

et al.

Nature Reviews Rheumatology, Journal Year: 2019, Volume and Issue: 15(12), P. 705 - 730

Published: Nov. 11, 2019

Language: Английский

Citations

465
WNT–β-catenin signalling — a versatile player in kidney injury and repair DOI

Stefan Schunk,

Jürgen Floege,

Danilo Fliser

et al.

Nature Reviews Nephrology, Journal Year: 2020, Volume and Issue: 17(3), P. 172 - 184

Published: Sept. 28, 2020

Language: Английский

Citations

301
Kidney fibrosis: from mechanisms to therapeutic medicines DOI Creative Commons

Rongshuang Huang,

Ping Fu, Liang Ma

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 17, 2023

Abstract Chronic kidney disease (CKD) is estimated to affect 10–14% of global population. Kidney fibrosis, characterized by excessive extracellular matrix deposition leading scarring, a hallmark manifestation in different progressive CKD; However, at present no antifibrotic therapies against CKD exist. fibrosis identified tubule atrophy, interstitial chronic inflammation and fibrogenesis, glomerulosclerosis, vascular rarefaction. Fibrotic niche, where organ initiates, complex interplay between injured parenchyma (like tubular cells) multiple non-parenchymal cell lineages (immune mesenchymal located spatially within scarring areas. Although the mechanisms are complicated due kinds cells involved, with help single-cell technology, many key questions have been explored, such as what kind renal tubules profibrotic, myofibroblasts originate, which immune how communicate each other. In addition, genetics epigenetics deeper that regulate fibrosis. And reversible nature epigenetic changes including DNA methylation, RNA interference, chromatin remodeling, gives an opportunity stop or reverse therapeutic strategies. More marketed (e.g., RAS blockage, SGLT2 inhibitors) developed delay progression recent years. Furthermore, better understanding also favored discover biomarkers fibrotic injury. review, we update advances mechanism summarize novel treatment for CKD.

Language: Английский

Citations

274
Randall’s plaque and calcium oxalate stone formation: role for immunity and inflammation DOI
Saeed R. Khan, Benjamin K. Canales, Paul R. Dominguez‐Gutierrez

et al.

Nature Reviews Nephrology, Journal Year: 2021, Volume and Issue: 17(6), P. 417 - 433

Published: Jan. 29, 2021

Language: Английский

Citations

259
Signaling pathways of chronic kidney diseases, implications for therapeutics DOI Creative Commons
Qian Yuan,

Ben Tang,

Chun Zhang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 9, 2022

Abstract Chronic kidney disease (CKD) is a chronic renal dysfunction syndrome that characterized by nephron loss, inflammation, myofibroblasts activation, and extracellular matrix (ECM) deposition. Lipotoxicity oxidative stress are the driving force for loss of including tubules, glomerulus, endothelium. NLRP3 inflammasome signaling, MAPK PI3K/Akt RAAS signaling involves in lipotoxicity. The upregulated Nox expression decreased Nrf2 result directly. injured resident cells release proinflammatory cytokines chemokines to recruit immune such as macrophages from bone marrow. NF-κB JAK-STAT Toll-like receptor cGAS-STING major pathways mediate inflammation inflammatory cells. produce secret great number profibrotic TGF-β1, Wnt ligands, angiotensin II. TGF-β Notch evoke activation promote generation ECM. potential therapies targeted these also introduced here. In this review, we update key lipotoxicity, stress, kidneys with injury, drugs based on latest studies. Unifying will be instrumental advance further basic clinical investigation CKD.

Language: Английский

Citations

220
The fibrogenic niche in kidney fibrosis: components and mechanisms DOI
Li Li, Haiyan Fu, Youhua Liu

et al.

Nature Reviews Nephrology, Journal Year: 2022, Volume and Issue: 18(9), P. 545 - 557

Published: July 4, 2022

Language: Английский

Citations

219
The Relationship Between Gut Microbiota and Inflammatory Diseases: The Role of Macrophages DOI Creative Commons
Ji Wang, Weidong Chen, Yan‐Dong Wang

et al.

Frontiers in Microbiology, Journal Year: 2020, Volume and Issue: 11

Published: June 9, 2020

Gut microbiota, an integral part of the human body, comprise bacteria, fungi, archaea, and protozoa. There is consensus that disruption gut microbiota (termed “gut dysbiosis”) influenced by host genetics, diet, antibiotics, inflammation, it closely linked to pathogenesis inflammatory diseases, such as obesity bowel disease (IBD). Macrophages are key players in maintenance tissue homeostasis eliminating invading pathogens exhibit extreme plasticity their phenotypes, M1 or M2, which have been demonstrated exert pro- anti-inflammatory functions. Microbiota-derived metabolites, short-chain fatty acids (SCFAs) Gram-negative bacterial lipopolysaccharides (LPS), pro-inflammatory effects acting on macrophages. Understanding role macrophages microbiota-inflammation interactions might provide us a novel method for preventing treating diseases. In this review, we summarize recent research relationship between inflammation discuss important context.

Language: Английский

Citations

212
Molecularly Engineered Macrophage‐Derived Exosomes with Inflammation Tropism and Intrinsic Heme Biosynthesis for Atherosclerosis Treatment DOI
Guanghao Wu, Jinfeng Zhang,

Qianru Zhao

et al.

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 59(10), P. 4068 - 4074

Published: Dec. 19, 2019

Atherosclerosis (AS) is a major contributor to cardiovascular diseases worldwide, and alleviating inflammation promising strategy for AS treatment. Here, we report molecularly engineered M2 macrophage-derived exosomes (M2 Exo) with inflammation-tropism anti-inflammatory capabilities imaging therapy. Exo are derived from macrophages further electroporated FDA-approved hexyl 5-aminolevulinate hydrochloride (HAL). After systematic administration, the exhibit excellent anti-inflammation effects via surface-bonded chemokine receptors cytokines released macrophages. Moreover, encapsulated HAL can undergo intrinsic biosynthesis metabolism of heme generate carbon monoxide bilirubin, which enhance finally alleviate AS. Meanwhile, intermediate protoporphyrin IX (PpIX) pathway permits fluorescence tracking

Language: Английский

Citations

209
Diverse Role of TGF-β in Kidney Disease DOI Creative Commons
Yue-Yu Gu, Xusheng Liu,

Xiao‐Ru Huang

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: Feb. 28, 2020

Inflammation and fibrosis are two pathological features of chronic kidney disease (CKD). Transforming growth factor-β (TGF-β) has been long considered as a key mediator renal fibrosis. In addition, TGF-β also acts potent anti-inflammatory cytokine that negatively regulates inflammation. Thus, blockade inhibits while promoting inflammation, revealing diverse role for in CKD. It is now well documented TGF-β1 activates its downstream signaling molecules such Smad3 Smad3-dependent non-coding RNAs to transcriptionally differentially regulate inflammation fibrosis, which regulated by Smad7. Therefore, treatments rebalancing Smad3/Smad7 or specifically targeting could be better therapeutic approach. this review, the paradoxical functions underlying mechanisms discussed novel strategies TGF-β/Smad transcriptomes highlighted.

Language: Английский

Citations

189