Inhibition of Yes-Associated Protein by Verteporfin Ameliorates Unilateral Ureteral Obstruction-Induced Renal Tubulointerstitial Inflammation and Fibrosis

Jin, Jong-Sik; Park, Woong; Li, Wenjia; Kim, Won; Park, Sung Kwang; Kang, Kyung Pyo

doi:10.3390/ijms21218184

Cited by 24 publications

(20 citation statements)

References 44 publications

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“…Apart from the mechanical difference, DTM components differences may also influence YAP1 intracellular distribution. TGF-β1, identified in DAF-G, was reported to mediate YAP1 activation via PI3K/Akt pathway, resulting in myofibroblasts phenotype [ 74 , 75 ]. YAP1 target gene subsets were also largely dependent on endogenous TGF-β1 signaling [ 76 ].…”

Section: Discussionmentioning

confidence: 99%

Decellularized Disc Hydrogels for hBMSCs tissue-specific differentiation and tissue regeneration

Peng

Xia

Lin

et al. 2021

Bioactive Materials

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Tissue specificity, a key factor in the decellularized tissue matrix (DTM), has shown bioactive functionalities in tuning cell fate—e.g., the differentiation of mesenchymal stem cells. Notably, cell fate is also determined by the living microenvironment, including material composition and spatial characteristics. Herein, two neighboring tissues within intervertebral discs, the nucleus pulposus (NP) and annulus fibrosus (AF), were carefully processed into DTM hydrogels (abbreviated DNP-G and DAF-G, respectively) to determine the tissue-specific effects on stem cell fate, such as specific components and different culturing methods, as well as in vivo regeneration. Distinct differences in their protein compositions were identified by proteomic analysis. Interestingly, the fate of human bone marrow mesenchymal stem cells (hBMSCs) also responds to both culturing methods and composition. Generally, hBMSCs cultured with DNP-G (3D) differentiated into NP-like cells, while hBMSCs cultured with DAF-G (2D) underwent AF-like differentiation, indicating a close correlation with the native microenvironments of NP and AF cells, respectively. Furthermore, we found that the integrin-mediated RhoA/LATS/YAP1 signaling pathway was activated in DAF-G (2D)-induced AF-specific differentiation. Additionally, the activation of YAP1 determined the tendency of NP- or AF-specific differentiation and played opposite regulatory effects. Finally, DNP-G and DAF-G specifically promoted tissue regeneration in NP degeneration and AF defect rat models, respectively. In conclusion, DNP-G and DAF-G can specifically determine the fate of stem cells through the integrin-mediated RhoA/LATS/YAP1 signaling pathway, and this tissue specificity is both compositional and spatial, supporting the utilization of tissue-specific DTM in advanced treatments of intervertebral disc degeneration.

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Section: Discussionmentioning

confidence: 99%

Decellularized Disc Hydrogels for hBMSCs tissue-specific differentiation and tissue regeneration

Peng

Xia

Lin

et al. 2021

Bioactive Materials

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“…Remarkably, YAP is upregulated in dystrophic mdx muscle, denervated muscle, and in hind-limbs from the SOD1G93A ALS model [ 122 , 128 ], then it is possible that YAP/TEAD can be contributing to CCN2/CTGF upregulation in fibrotic skeletal muscle, in a direct way and by crosstalking with TGF-β, LPA and hypoxia/vasculogenesis pathways. As a possible therapeutic target for kidney diseases, YAP inhibition using verteporfin effectively decreased renal fibrosis in mice, reducing TGF-β signaling and CCN2/CTGF levels [ 129 ]. Additional investigation must be performed to fully determine the contribution of YAP/TEAD on CCN2/CTGF modulation in fibrotic skeletal muscle.…”

Section: Regulation Of Ccn2/ctgf and Fibrosis In Skeletal Muscle: Role Of Vasoactive Peptidesmentioning

confidence: 99%

Role of Matricellular CCN Proteins in Skeletal Muscle: Focus on CCN2/CTGF and Its Regulation by Vasoactive Peptides

Rebolledo

Acuña

Brandan

2021

IJMS

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The Cellular Communication Network (CCN) family of matricellular proteins comprises six proteins that share conserved structural features and play numerous biological roles. These proteins can interact with several receptors or soluble proteins, regulating cell signaling pathways in various tissues under physiological and pathological conditions. In the skeletal muscle of mammals, most of the six CCN family members are expressed during embryonic development or in adulthood. Their roles during the adult stage are related to the regulation of muscle mass and regeneration, maintaining vascularization, and the modulation of skeletal muscle fibrosis. This work reviews the CCNs proteins’ role in skeletal muscle physiology and disease, focusing on skeletal muscle fibrosis and its regulation by Connective Tissue Growth factor (CCN2/CTGF). Furthermore, we review evidence on the modulation of fibrosis and CCN2/CTGF by the renin-angiotensin system and the kallikrein-kinin system of vasoactive peptides.

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“…Silencing YAP in early embryonic nephron progenitor cells leads to hypoplastic kidney, and TAZ knockout mice show impairment of renal epithelial cell cilia, resulting in polycystic kidneys (17,18). In addition, YAP/TAZ inhibition by verteporfin ameliorates renal fibrosis after unilateral ureteral obstruction in adult mice (19).…”

Section: Introductionmentioning

confidence: 99%

Hyperactivation of YAP/TAZ drives alterations in mesangial cells through stabilization of N-MYC in diabetic nephropathy

Choi

Suh

Bae

et al. 2022

Preprint

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Mesangial cells (MCs) in the kidney are central to maintaining glomerular integrity, and their impairment leads to major glomerular diseases including diabetic nephropathy (DN). Although high blood glucose elicits abnormal alterations in MCs, the underlying molecular mechanism is poorly understood. Here, we show that YAP and TAZ, the final effectors of the Hippo pathway, are highly increased in MCs of patients with DN and of Zucker diabetic fatty rats. Moreover, high glucose directly induces activation of YAP/TAZ through the canonical Hippo pathway in cultured MCs. Hyperactivation of YAP/TAZ in mouse model MCs recapitulates the hallmarks of DN, including excessive proliferation of MCs and extracellular matrix deposition, endothelial cell impairment, glomerular sclerosis, albuminuria, and reduced glomerular filtration rate. Mechanistically, activated YAP/TAZ bind and stabilize N-Myc protein, one of the Myc family of oncogenes. N-Myc stabilization leads to aberrant enhancement of its transcriptional activity and eventually to MC impairments and DN pathogenesis. Together, these findings shed light on how high blood glucose in diabetes mellitus leads to DN and support a rationale that lowering blood glucose in diabetes mellitus could delay DN pathogenesis.

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Inhibition of Yes-Associated Protein by Verteporfin Ameliorates Unilateral Ureteral Obstruction-Induced Renal Tubulointerstitial Inflammation and Fibrosis

Cited by 24 publications

References 44 publications

Decellularized Disc Hydrogels for hBMSCs tissue-specific differentiation and tissue regeneration

Decellularized Disc Hydrogels for hBMSCs tissue-specific differentiation and tissue regeneration

Role of Matricellular CCN Proteins in Skeletal Muscle: Focus on CCN2/CTGF and Its Regulation by Vasoactive Peptides

Hyperactivation of YAP/TAZ drives alterations in mesangial cells through stabilization of N-MYC in diabetic nephropathy

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