Src Family Kinases: A Potential Therapeutic Target for Acute Kidney Injury

Li, Nannan; Lin, Guoxin; Zhang, Hao; Sun, Jian; Gui, Ming; Liu, Yan; Li, Wei; Liu, Jishi; Tang, Juan

doi:10.3390/biom12070984

Cited by 15 publications

(10 citation statements)

References 153 publications

(226 reference statements)

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“…c‐Src belongs to the Src family of tyrosine kinases (SFKs) and shares structural homology with other family members, including Fyn, c‐Yes, Lck, and Fgr. [ 42 , 43 ] In SFKs, all members have a highly conserved tyrosine residue (Tyr530 in c‐Src) in the tail region that once phosphorylated, remains in an inactive conformation. [ 36 , 44 ] However, the N‐terminal unique domain, which is the only non‐conserved region within the kinase family, is specific to c‐Src.…”

Section: Discussionmentioning

confidence: 99%

The c‐Src/LIST Positive Feedback Loop Sustains Tumor Progression and Chemoresistance

Wang

et al. 2023

Advanced Science

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Chemotherapy resistance and treatment failure hinder clinical cancer treatment. Src, the first mammalian proto‐oncogene to be discovered, is a valuable anti‐cancer therapeutic target. Although several c‐Src inhibitors have reached the clinical stage, drug resistance remains a challenge during treatment. Herein, a positive feedback loop between a previously uncharacterized long non‐coding RNA (lncRNA), which the authors renamed lncRNA‐inducing c‐Src tumor‐promoting function (LIST), and c‐Src is uncovered. LIST directly binds to and regulates the Y530 phosphorylation activity of c‐Src. As a c‐Src agonist, LIST promotes tumor chemoresistance and progression in vitro and in vivo in multiple cancer types. c‐Src can positively regulate LIST transcription by activating the NF‐κB signaling pathway and then recruiting the P65 transcription factor to the LIST promoter. Interestingly, the LIST/c‐Src interaction is associated with evolutionary new variations of c‐Src. It is proposed that the human‐specific LIST/c‐Src axis renders an extra layer of control over c‐Src activity. Additionally, the LIST/c‐Src axis is of high physiological relevance in cancer and may be a valuable prognostic biomarker and potential therapeutic target.

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Section: Discussionmentioning

confidence: 99%

The c‐Src/LIST Positive Feedback Loop Sustains Tumor Progression and Chemoresistance

Wang

et al. 2023

Advanced Science

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“…Src family kinases (SFKs) play a key role in regulating the autophagy of renal resident cells. [ 19 ] Thus, we assessed the expression patterns of SFKs in the podocytes treated with HG with or without NCOA3 lentivirus. Our results showed that among SFKs, only the mRNA level of Fyn was induced by HG, and downregulated by NCOA3 overexpression significantly ( Figure 3 A ).…”

Section: Resultsmentioning

confidence: 99%

Deficiency of Nuclear Receptor Coactivator 3 Aggravates Diabetic Kidney Disease by Impairing Podocyte Autophagy

Xie,

Yuan,

Cao

et al. 2024

Advanced Science

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Nuclear receptors (NRs) are important transcriptional factors that mediate autophagy, preventing podocyte injury and the progression of diabetic kidney disease (DKD). However, the role of nuclear receptor coactivators that are powerful enhancers for the transcriptional activity of NRs in DKD remains unclear. In this study, a significant decrease in Nuclear Receptor Coactivator 3 (NCOA3) is observed in injured podocytes caused by high glucose treatment. Additionally, NCOA3 overexpression counteracts podocyte damage by improving autophagy. Further, Src family member, Fyn is identified to be the target of NCOA3 that mediates the podocyte autophagy process. Mechanistically, NCOA3 regulates the transcription of Fyn in a nuclear receptor, PPAR‐γ dependent way. Podocyte‐specific NCOA3 knockout aggravates albuminuria, glomerular sclerosis, podocyte injury, and autophagy in DKD mice. However, the Fyn inhibitor, AZD0530, rescues podocyte injury of NCOA3 knockout DKD mice. Renal NCOA3 overexpression with lentivirus can ameliorate podocyte damage and improve podocyte autophagy in DKD mice. Taken together, the findings highlight a novel target, NCOA3, that protects podocytes from high glucose injury by maintaining autophagy.

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“…Li et al highlighted the significance of the Lyn family of SFKs. Lyn is of particular importance because its deficiency has led to the pathogenesis of many different diseases [302]. For instance, in mice, Lyn knockout exacerbates lipopolysaccharide-induced lung inflammation, and the mechanism involves NF-κB activation [303].…”

Section: Src Family Kinasesmentioning

confidence: 99%

Fibrosis in Chronic Kidney Disease: Pathophysiology and Therapeutic Targets

Reiss,

Jacob,

Zubair

et al. 2024

JCM

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Chronic kidney disease (CKD) is a slowly progressive condition characterized by decreased kidney function, tubular injury, oxidative stress, and inflammation. CKD is a leading global health burden that is asymptomatic in early stages but can ultimately cause kidney failure. Its etiology is complex and involves dysregulated signaling pathways that lead to fibrosis. Transforming growth factor (TGF)-β is a central mediator in promoting transdifferentiation of polarized renal tubular epithelial cells into mesenchymal cells, resulting in irreversible kidney injury. While current therapies are limited, the search for more effective diagnostic and treatment modalities is intensive. Although biopsy with histology is the most accurate method of diagnosis and staging, imaging techniques such as diffusion-weighted magnetic resonance imaging and shear wave elastography ultrasound are less invasive ways to stage fibrosis. Current therapies such as renin-angiotensin blockers, mineralocorticoid receptor antagonists, and sodium/glucose cotransporter 2 inhibitors aim to delay progression. Newer antifibrotic agents that suppress the downstream inflammatory mediators involved in the fibrotic process are in clinical trials, and potential therapeutic targets that interfere with TGF-β signaling are being explored. Small interfering RNAs and stem cell-based therapeutics are also being evaluated. Further research and clinical studies are necessary in order to avoid dialysis and kidney transplantation.

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Src Family Kinases: A Potential Therapeutic Target for Acute Kidney Injury

Cited by 15 publications

References 153 publications

The c‐Src/LIST Positive Feedback Loop Sustains Tumor Progression and Chemoresistance

The c‐Src/LIST Positive Feedback Loop Sustains Tumor Progression and Chemoresistance

Deficiency of Nuclear Receptor Coactivator 3 Aggravates Diabetic Kidney Disease by Impairing Podocyte Autophagy

Fibrosis in Chronic Kidney Disease: Pathophysiology and Therapeutic Targets

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