Uremic toxin indoxyl sulfate induces dysfunction of vascular smooth muscle cells via integrin-β1/ERK signaling pathway

Yu, Haibo; Zhou, Chunyu; D, Hu; Li, Changbin; Wang, Qiang; Yang, Sihua; Peng, Ai

doi:10.1007/s10157-022-02195-z

Cited by 1 publication

(1 citation statement)

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“…IxS upregulates ITGβ1 (integrin β1) in HUVSMCs (human umbilical vein smooth muscle cells) with downstream activation of the ERK signaling pathway, which promoted focal adhesion, migration, and proliferation of SMCs. 140 Medial wall calcification is a typical feature of uremia-associated vasculopathy and results from an active, cell-mediated process in which VSMCs change their contractile phenotype to an osteogenic phenotype resembling osteogenesis in bone. 141 In this process, the induction of ROS production and changes in VSMC sensitivity to PDGF-β (platelet-derived growth factor beta) play a central role.…”

Section: Compendium On Increased Risk Of Cardiovascular Complications...mentioning

confidence: 99%

Role of the Microbiome in Gut-Heart-Kidney Cross Talk

Glorieux

Nigám

Vanholder

et al. 2023

Circulation Research

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Homeostasis is a prerequisite for health. When homeostasis becomes disrupted, dysfunction occurs. This is especially the case for the gut microbiota, which under normal conditions lives in symbiosis with the host. As there are as many microbial cells in and on our body as human cells, it is unlikely they would not contribute to health or disease. The gut bacterial metabolism generates numerous beneficial metabolites but also uremic toxins and their precursors, which are transported into the circulation. Barrier function in the intestine, the heart, and the kidneys regulates metabolite transport and concentration and plays a role in inter-organ and inter-organism communication via small molecules. This communication is analyzed from the perspective of the remote sensing and signaling theory, which emphasizes the role of a large network of multispecific, oligospecific, and monospecific transporters and enzymes in regulating small-molecule homeostasis. The theory provides a systems biology framework for understanding organ cross talk and microbe-host communication involving metabolites, signaling molecules, nutrients, antioxidants, and uremic toxins. This remote small-molecule communication is critical for maintenance of homeostasis along the gut-heart-kidney axis and for responding to homeostatic perturbations. Chronic kidney disease is characterized by gut dysbiosis and accumulation of toxic metabolites. This slowly impacts the body, affecting the cardiovascular system and contributing to the progression of kidney dysfunction, which in its turn influences the gut microbiota. Preserving gut homeostasis and barrier functions or restoring gut dysbiosis and dysfunction could be a minimally invasive way to improve patient outcomes and quality of life in many diseases, including cardiovascular and kidney disease.

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Section: Compendium On Increased Risk Of Cardiovascular Complications...mentioning

confidence: 99%