ArticleKidney international2022
Modulation of transforming growth factor-β-induced kidney fibrosis by leucine-rich ⍺-2 glycoprotein-1.
Article in Kidney international, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 88 citations in OpenAlex.
- Compensatory Mitophagy via NEDD4/HIF-1α/BNIP3 Pathway Restrains EndMT and Renal Allograft Interstitial Fibrosis Induced by TNFα.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Twist Family BHLH Transcription Factor 1 orchestrates hypoxia-lactate crosstalk to bridge glycolytic flux and tubular maladaptation in fibrotic kidneys.Molecular biomedicine · 2026Article
- Intracellular LRG1 recruits MARCH2 to ubiquitinate and degrade endothelial VE-cadherin in septic lung injury.Acta pharmacologica Sinica · 2026Article
- A TGF-β1/LEF1/β-catenin/JLP network motif regulates autophagy and tubule injury in renal fibrosis.JCI insight · 2026Article
- Molecular mechanisms and novel therapeutic targets of diabetic kidney disease.Chinese medical journal · 2026Review
- Association of triglyceride-glucose index and triglyceride-glucose body mass index with risk and prognosis of chronic obstructive pulmonary disease: a systematic review and meta-analysis.Journal of thoracic disease · 2026Article
- LRG1 as a Potential Therapeutic Target in Atherosclerosis: Mechanistic Basis and Current Evidence.Cells · 2026Review
- TGF-β1 induces epithelial-mesenchymal transition and fibrosis of ureteral epithelial cells via targeting RACK1 in ureteropelvic junction obstruction.Translational pediatrics · 2026Article
- FOS drives podocyte injury and renal fibrosis in diabetic kidney disease via direct Smad3 binding.Cellular and molecular life sciences : CMLS · 2026Article
- Elevated leucine-rich alpha-2 glycoprotein levels and mortality risk in end-stage renal disease: evidence for gender differences.Clinical kidney journal · 2026Article
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Cartilage intermediate layer protein inhibits ligamentum flavum hypertrophy mediated by TGF-β1/SMAD3/SERPINE2 signaling pathway.Cellular and molecular life sciences : CMLS · 2026Article
- The role of the vascular niche in regulating kidney tubulointerstitial fibrosis.Kidney international · 2026Review
- Revealing the multiple faces of LRG1: gene expression, structure, function, and therapeutic potential.Journal of advanced research · 2026Review
- Functional Molecular Plasma Biomarkers of Inflammation and Repair in Kidney Disease Progression in Gum Arabica Modality of CKD.International journal of molecular sciences · 2026Article
- Diabetes and its complications: molecular mechanisms, prevention and treatment.Signal transduction and targeted therapy · 2026Review
- CILP attenuates pulmonary fibrosis through the TGF-β1/SMAD3 pathway.European journal of medical research · 2025Article
- Integrative transcriptomic and genomic insights into diabetic kidney disease: evidence from multi-omics analysis and experimental validation.Renal failure · 2025Article
- The critical role of LRG1 in pathological fibrosis.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Tubular Injury in Diabetic Kidney Disease: Early Diagnosis and Intervention Strategies.Diabetes/metabolism research and reviews · 2025Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Kidney fibrosis is considered the final convergent pathway for progressive chronic kidney diseases, but there is still a paucity of success in clinical application for effective therapy. We recently demonstrated that the expression of secreted leucine-rich α-2 glycoprotein-1 (LRG1) is associated with worsened kidney outcomes in patients with type 2 diabetes and that LRG1 enhances endothelial transforming growth factor-β signaling to promote diabetic kidney disease progression. While the increased expression of LRG1 was most prominent in the glomerular endothelial cells in diabetic kidneys, its increase was also observed in the tubulointerstitial compartment. Here, we explored the potential role of LRG1 in kidney epithelial cells and TGF-β-mediated tubulointerstitial fibrosis independent of diabetes. LRG1 expression was induced by tumor necrosis factor-α in cultured kidney epithelial cells and potentiated TGF-β/Smad3 signal transduction. Global Lrg1 loss in mice led to marked attenuation of tubulointerstitial fibrosis in models of unilateral ureteral obstruction and aristolochic acid fibrosis associated with concomitant decreases in Smad3 phosphorylation in tubule epithelial cells. In mice with kidney epithelial cell-specific LRG1 overexpression, while no significant phenotypes were observed at baseline, marked exacerbation of tubulointerstitial fibrosis was observed in the obstructed kidneys. This was associated with enhanced Smad3 phosphorylation in both kidney epithelial cells and α-smooth muscle actin-positive interstitial cells. Co-culture of kidney epithelial cells with primary kidney fibroblasts confirmed the potentiation of TGF-β-mediated Smad3 activation in kidney fibroblasts through epithelial-derived LRG1. Thus, our results indicate that enhanced LRG1 expression-induced epithelial injury is an amplifier of TGF-β signaling in autocrine and paracrine manners promoting tubulointerstitial fibrosis. Hence, therapeutic targeting of LRG1 may be an effective means to curtail kidney fibrosis progression in chronic kidney disease.
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