ArticleArthritis & rheumatology (Hoboken, N.J.)2025
Hypoxia Promotes the Expression of ADAM9 by Tubular Epithelial Cells, Which Enhances Transforming Growth Factor β1 Activation and Promotes Tissue Fibrosis in Patients With Lupus Nephritis.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Cellular crosstalk of fibroblast-myofibroblast transition in intestinal homeostasis and disease.Biomarker research · 2026Review
- Urinary Exosomes as Potential Biomarkers for Diagnosis, Disease Activity Assessment, Treatment Monitoring, and Prognosis in Lupus Nephritis.International journal of molecular sciences · 2026Review
- Dangguibuxue Decoction Attenuated AA I-Induced Renal Fibrosis: Integrating Network Pharmacology and Experimental Validation.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Endothelial soluble APP/APLP2 promote heart repair through KIT-mediated angiogenesis.Science advances · 2026Article
- ADAM9 in tumor biology: molecular functions, clinical implications, and therapeutic targeting.Cellular & molecular biology letters · 2026Review
- ADAM9 Promotes Glycolysis in Th17 Cells and Autoimmunity Through Activation of IGF-1 Signaling.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Urinary extracellular vesicle RNAs as novelClinical kidney journal · 2025Article
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Abstract
objectiveEnhanced expression of transforming growth factor (TGF) β in the kidneys of patients with lupus nephritis (LN) can lead to progressive fibrosis, resulting in end-organ damage. ADAM9 activates TGFβ1 by cleaving the latency-associated peptide (LAP). We hypothesized that ADAM9 in the kidney may accelerate fibrogenesis by activating TGFβ1.
methodsWe assessed the expression of ADAM9 in the kidneys of mice and humans who were lupus prone. In vitro experiments were conducted using tubular epithelial cells (TECs) isolated from mice and explored the mechanisms responsible for the up-regulation of ADAM9 and the subsequent activation of TGFβ1. To assess the role of ADAM9 in the development of tubular-intestinal fibrosis in individuals with LN, we generated MRL/lpr mice who were Adam9 deficient.
resultsADAM9 was highly expressed in tubules from MRL/lpr mice. The transcription factor hypoxia-inducible factor-1α was found to promote the transcription of ADAM9 in TECs. TECs from mice who were Adam9 deficient and exposed to the hypoxia mimetic agent dimethyloxalylglycine failed to cleave the LAP to produce bioactive TGFβ1 from latent TGFβ1. Coculture of TECs from mice who were Adam9 deficient with fibroblasts in the presence of dimethyloxalylglycine and latent TGFβ1 produced decreased amounts of type I collagen and α-smooth muscle actin (SMA) by fibroblasts. MRL/lpr mice who were Adam9 deficient showed reduced interstitial fibrosis. At the translational level, ADAM9 expression in tissues and urine of patients with LN was found to increase.
conclusionHypoxia promotes the expression of ADAM9 by TECs, which is responsible for the development of interstitial fibrosis in patients with LN by enhancing the TGFβ1 activation, which promotes fibroblasts to produce collagen and α-SMA.
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