Blocking AURKA with MK-5108 attenuates renal fibrosis in chronic kidney disease

Jiang, Meiyan; Bai, Mei; Xu, Shuang; Wang, Ting; Lei, Juan; Xu, Man; Huang, Songming; Zhang, Aihua

doi:10.1016/j.bbadis.2021.166227

Cited by 5 publications

(2 citation statements)

References 41 publications

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“…Therefore, it is essential to focus on inhibiting EMT to reduce fibrosis 43 . Focusing on this aspect, Jiang et al observed that an AURKA blocker (MK‐5108) showed attenuating activity against EMT, thereby reducing kidney fibrosis 44 . Since AURKA plays an integral role in Plk1 activation, blocking AURKA can lead to Plk1 inhibition, which ultimately alleviates kidney fibrosis, commonly occurring in CKD.…”

Section: The Crucial Nexus Of Plk1 In the Development And Progression...mentioning

confidence: 99%

Targeting polo‐like kinase 1 to treat kidney diseases

Kulkarni,

Dagar,

Gaikwad

2024

Cell Biochemistry & Function

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Globally, ∼850 million individuals suffer from some form of kidney disease. This staggering figure underscores the importance of continued research and innovation in the field of nephrology to develop effective treatments and improve overall global kidney health. In current research, the polo‐like kinase (Plk) family has emerged as a group of highly conserved enzyme kinases vital for proper cell cycle regulation. Plks are defined by their N‐terminal kinase domain and C‐terminal polo‐box domain, which regulate their catalytic activity, subcellular localization, and substrate recognition. Among the Plk family members, Plk1 has garnered significant attention due to its pivotal role in regulating multiple mitotic processes, particularly in the kidneys. It is a crucial serine–threonine (Ser‐Thr) kinase involved in cell division and genomic stability. In this review, we delve into the types and functions of Plks, focusing on Plk1's significance in processes such as cell proliferation, spindle assembly, and DNA damage repair. The review also underscores Plk1's vital contributions to maintaining kidney homeostasis, elucidating its involvement in nuclear envelope breakdown, anaphase‐promoting complex/cyclosome activation, and the regulation of mRNA translation machinery. Furthermore, the review discusses how Plk1 contributes to the development and progression of kidney diseases, emphasizing its overexpression in conditions such as acute kidney injury, chronic kidney disease, and so forth. It also highlights the importance of exploring Plk1 modulators as targeted therapies for kidney diseases in future. This review will help in understanding the role of Plk1 in kidney disease development, paving the way for the discovery and development of novel therapeutic approaches to manage kidney diseases effectively.

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Section: The Crucial Nexus Of Plk1 In the Development And Progression...mentioning

confidence: 99%

Targeting polo‐like kinase 1 to treat kidney diseases

Kulkarni,

Dagar,

Gaikwad

2024

Cell Biochemistry & Function

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“…It is noteworthy that activated macrophages have the capability to release TGF-β1, a key transforming factor that plays a significant role in renal fibrosis. TGF-β1 is involved in various processes, including the promotion of the conversion of hematopoietic stem cells into fibroblasts, enhancement of renal fibroblast maturation, and stimulation of the transformation of renal capillary endothelial cells, renal tubular epithelial cells, and mesangial cells into mesenchymal fibroblasts [ [35] , [36] , [37] ]. Chen et al [ 38 ] found that histone deacetylase 6 (HDAC6) inhibitors inhibited TGF-β1 and epidermal growth factor receptor (EGFR) signaling pathways in obstructive nephropathy to delay the development of renal fibrosis, suggesting that HDAC6 may become a potential target for the treatment of renal fibrosis.…”

Section: The Mechanism Of Renal Interstitial Fibrosis In Obstructive ...mentioning

confidence: 99%

Research progress on the mechanism of renal interstitial fibrosis in obstructive nephropathy

Wang

Liao

Chen

2023

Heliyon

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Meis1 Targets Protein Tyrosine Phosphatase Receptor J in Fibroblast to Retard Chronic Kidney Disease Progression

Bai,

Xu,

Jiang

et al. 2024

Advanced Science

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Renal fibrosis is a common pathological feature of chronic kidney disease (CKD) with the proliferation and activation of myofibroblasts being definite effectors and drivers. Here, increased expression of Meis1 (myeloid ecotropic viral integration site 1) is observed, predominantly in the nucleus of the kidney of CKD patients and mice, and negatively correlates with serum creatinine. Fibroblast‐specific knock‐in of Meis1 inhibits myofibroblast activation and attenuates renal fibrosis and kidney dysfunction in CKD models. Overexpression of Meis1 in NRK‐49F cells suppresses the pro‐fibrotic response induced by transforming growth factor‐β1 but accelerates by its knockdown. Mechanistically, Meis1 targets protein tyrosine phosphatase receptor J (Ptprj) to block renal fibrosis by inhibiting the proliferation and activation of fibroblasts. Finally, a new activator of Ptprj is identified through computer‐aided virtual screening, which has the effect of alleviating renal fibrosis. Collectively, these results illustrate that the Meis1/Ptprj axis has therapeutic potential for clinically treating CKD.

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Blocking AURKA with MK-5108 attenuates renal fibrosis in chronic kidney disease

Cited by 5 publications

References 41 publications

Targeting polo‐like kinase 1 to treat kidney diseases

Targeting polo‐like kinase 1 to treat kidney diseases

Research progress on the mechanism of renal interstitial fibrosis in obstructive nephropathy

Meis1 Targets Protein Tyrosine Phosphatase Receptor J in Fibroblast to Retard Chronic Kidney Disease Progression

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