ArticleFrontiers in pharmacology2019
Combined Blockade of Smad3 and JNK Pathways Ameliorates Progressive Fibrosis in Folic Acid Nephropathy.
Article in Frontiers in pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 2 of them syntheses that pooled it.
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Who cites it
17 citing papers in PubMed, 2 syntheses or guidelines pooled it, 31 citations in OpenAlex.
- TGF-β/Smad Signaling Pathway in Tubulointerstitial Fibrosis.Frontiers in pharmacology · 2022Pooled it
- Pooled it
- Ablation of the renal tubular gluconeogenic enzyme PCK1 drives AKI-to-CKD transition by negatively regulating the TGF-β/Smad3 signaling pathway.Cellular and molecular life sciences : CMLS · 2026Article
- Azilsartan as a novel anti-ferriptotic agent via the upregulation of the Nrf2/HO-1/SLC7A11/GPX4 axis and downregulation of inflammatory pathways in folic acid-induced acute kidney injury in male mice.Toxicology reports · 2026Article
- The role of JNK signaling pathway in organ fibrosis.Journal of advanced research · 2025Review
- Citronellol protects renal function by exerting anti-inflammatory and antiapoptotic effects against acute kidney injury induced by folic acid in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- A new Jun amino-terminal kinase inhibitor, KRev-202, inhibits rat ischemic acute injury and the progression to renal fibrosis.Frontiers in pharmacology · 2025Article
- Drugs targeting TGF-β/Notch interaction attenuate hypertrophic scar formation by optic atrophy 1-mediated mitochondrial fusion.Molecular and cellular biochemistry · 2024Article
- The secreted micropeptide C4orf48 enhances renal fibrosis via an RNA-binding mechanism.The Journal of clinical investigation · 2024Article
- Mitochondrial quality control in acute kidney disease.Journal of nephrology · 2023Review
- Role of C-Reactive Protein in Kidney Diseases.Kidney diseases (Basel, Switzerland) · 2023Review
- Fibrosis: Types, Effects, Markers, Mechanisms for Disease Progression, and Its Relation with Oxidative Stress, Immunity, and Inflammation.International journal of molecular sciences · 2023Review
- PGC1Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022Article
- Folic acid-induced animal model of kidney disease.Animal models and experimental medicine · 2021Review
- Smad3-Targeted Therapy Protects against Cisplatin-Induced AKI by Attenuating Programmed Cell Death and Inflammation via a NOX4-Dependent Mechanism.Kidney diseases (Basel, Switzerland) · 2021Article
- c-Jun Amino Terminal Kinase Signaling Promotes Aristolochic Acid-Induced Acute Kidney Injury.Frontiers in physiology · 2021Article
- Propofol Attenuates Hypoxia/Reoxygenation-Induced Apoptosis and Autophagy in HK-2 Cells by Inhibiting JNK Activation.Yonsei medical journal · 2019Article
Corrections and comments
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Authors and funding
17 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute kidney injury leading to chronic kidney disease through tubulointerstitial fibrosis is a major challenge in nephropathy. Several signaling pathways promote interstitial fibrosis; however, effective suppression of fibrosis may require blockade of more than one pathway. This study investigated whether blockade of Smad3 and c-Jun N-terminal kinase (JNK) signaling gives added suppression of interstitial fibrosis in folic acid nephropathy. A single high dose of folic acid (FA) causes acute tubular damage in C57BL/6J mice followed by interstitial fibrosis and chronic renal impairment. Co-activations of Smad3 and JNK signaling occur in both tubular epithelial cells and myofibroblasts in areas of tubulointerstitial damage and fibrosis in both murine FA-induced nephropathy and human IgA nephropathy. Groups of mice were treated with a Smad3 inhibitor (SIS3), a JNK inhibitor (SP600125), or a combination from day 6 after FA administration until being killed on day 28. Each drug efficiently inhibited its specific target (Smad3 phosphorylation or c-Jun phosphorylation) without affecting the other pathway. Given alone, each drug partially reduced renal fibrosis, whereas the combination therapy gave an additive and profound protection from renal fibrosis and improved renal function. Inhibition of Smad3 and/or JNK signaling activities prevented down-regulation of PGC-1α in tubular epithelial cells and up-regulation of PGC-1α in myofibroblasts during FA-induced renal fibrosis and inflammation. The expression of PGC-1α was upregulated in
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