ArticleThe Journal of clinical investigation2017
Pericyte MyD88 and IRAK4 control inflammatory and fibrotic responses to tissue injury.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 145 citations in OpenAlex.
- Mechanisms of regeneration and maladaptive repair in acute kidney injury.Nature reviews. Nephrology · 2026Review
- A heterobifunctional IRAK4-targeting degrader impairs myddosome signaling in acute kidney injury and ameliorates kidney fibrosis.Communications biology · 2026Article
- MicroRNA210 regulated brain pericyte dysfunction exacerbates hypoxic-ischemic brain injury in neonatal mice.Fluids and barriers of the CNS · 2026Article
- The role of extracellular vesicles in kidney disease progression.Kidney research and clinical practice · 2026Article
- A biomimetic senotherapy replenishing MAT2A promotes wound regeneration in preclinical models.Nature communications · 2025Article
- Mitigating Methotrexate-Induced Kidney Damage in Mice by theACS omega · 2025Article
- Pericytes in tissue fibrosis.American journal of physiology. Cell physiology · 2025Review
- Immune control of brain physiology.Nature reviews. Immunology · 2025Review
- Bidirectional Role of Pericytes in Ischemic Stroke.Brain sciences · 2025Review
- Pericytes in the Development and Progression of Brain Diseases.Aging and disease · 2025Review
- Review
- Article
- STING Activation in Macrophages and Microglia Drives Poststroke Inflammation: Implications for Neuroinflammatory Mechanisms and Therapeutic Interventions.CNS neuroscience & therapeutics · 2024Article
- Therapy Targeted to the NLRP3 Inflammasome in Chronic Kidney Disease.Kidney diseases (Basel, Switzerland) · 2024Review
- ADAMTS12 promotes fibrosis by restructuring extracellular matrix to enable activation of injury-responsive fibroblasts.The Journal of clinical investigation · 2024Article
- Targeting inflammation in perivascular cells and neuroimmune interactions for treating kidney disease.Clinical and experimental nephrology · 2024Review
- Review
- The role of cardiac pericytes in health and disease: therapeutic targets for myocardial infarction.Nature reviews. Cardiology · 2024Review
- Deficiency of NLRP3 protects cerebral pericytes and attenuates Alzheimer's pathology in tau-transgenic mice.Frontiers in cellular neuroscience · 2024Article
- Mechanisms of inflammation modulation by different immune cells in hypertensive nephropathy.Frontiers in immunology · 2024Review
13 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Fibrotic disease is associated with matrix deposition that results in the loss of organ function. Pericytes, the precursors of myofibroblasts, are a source of pathological matrix collagens and may be promising targets for treating fibrogenesis. Here, we have shown that pericytes activate a TLR2/4- and MyD88-dependent proinflammatory program in response to tissue injury. Similarly to classic immune cells, pericytes activate the NLRP3 inflammasome, leading to IL-1β and IL-18 secretion. Released IL-1β signals through pericyte MyD88 to amplify this response. Unexpectedly, we found that MyD88 and its downstream effector kinase IRAK4 intrinsically control pericyte migration and conversion to myofibroblasts. Specific ablation of MyD88 in pericytes or pharmacological inhibition of MyD88 signaling by an IRAK4 inhibitor in vivo protected against kidney injury by profoundly attenuating tissue injury, activation, and differentiation of myofibroblasts. Our data show that in pericytes, MyD88 and IRAK4 are key regulators of 2 major injury responses: inflammatory and fibrogenic. Moreover, these findings suggest that disruption of this MyD88-dependent pathway in pericytes might be a potential therapeutic approach to inhibit fibrogenesis and promote regeneration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.