Antifibrotic role of PGC-1α-siRNA against TGF-β1-induced renal interstitial fibrosis

Wang, Jue‐Long; Chen, Chin-Wang; Tsai, Mu-Rou; Liu, Shufen; Hung, Tsung-Jeu; Yu-Ju-Hung,; Chang, Wen‐Cheng; Shi, Ming-Der; Hsieh, Pei-Fang; Yang, Yu‐Lin

doi:10.1016/j.yexcr.2018.06.016

Cited by 15 publications

(7 citation statements)

References 52 publications

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“…RNA interference technique is an emerging therapeutic by which messenger RNA (mRNA) could be degraded selectively and the expression of specific proteins was inhibited ( Saw and Song, 2020 ). Hence, RNAi is involved in renal fibrosis by inhibiting the overexpression of related genes, most commonly TGF-β1 ( Takabatake et al, 2005 ) along with its downstream genes, such as CTGF ( Ren et al, 2015 ) and proliferator-activated receptor coactivator-1 alpha (PGC-1α) ( Wang et al, 2018 ) and phosphorylation of Drp1 at serine 616 (p-Drp1S616) ( Wang et al, 2020b ). Researchers found that small interfering RNA (siRNA)-mediated gene silencing effectively suppressed the expression of corresponding mRNA and protein and thus significantly inhibited the secretion of fibrogenic factors and delay the progression of renal fibrosis ( Khaja et al, 2016 ; Isaka, 2018 ).…”

Section: New Therapies For Renal Fibrosismentioning

confidence: 99%

Signaling Pathways Involved in Diabetic Renal Fibrosis

Zhang

Jin

Kang

et al. 2021

Front. Cell Dev. Biol.

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Diabetic kidney disease (DKD), as the most common complication of diabetes mellitus (DM), is the major cause of end-stage renal disease (ESRD). Renal interstitial fibrosis is a crucial metabolic change in the late stage of DKD, which is always considered to be complex and irreversible. In this review, we discuss the pathological mechanisms of diabetic renal fibrosis and discussed some signaling pathways that are closely related to it, such as the TGF-β, MAPK, Wnt/β-catenin, PI3K/Akt, JAK/STAT, and Notch pathways. The cross-talks among these pathways were then discussed to elucidate the complicated cascade behind the tubulointerstitial fibrosis. Finally, we summarized the new drugs with potential therapeutic effects on renal fibrosis and listed related clinical trials. The purpose of this review is to elucidate the mechanisms and related pathways of renal fibrosis in DKD and to provide novel therapeutic intervention insights for clinical research to delay the progression of renal fibrosis.

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Section: New Therapies For Renal Fibrosismentioning

confidence: 99%

Signaling Pathways Involved in Diabetic Renal Fibrosis

Zhang

Jin

Kang

et al. 2021

Front. Cell Dev. Biol.

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“…In the present study, CXXC5 was an upstream regulator of PGC-1α possibly through an indirect effect. Since CXXC5 positively regulated p38 MAPK and Akt activation, and enhanced PGC-1α expression was achieved by the PI3K/Akt and p38 MAPK signaling, we tended to believe that Akt and p38 were “bridges” to link upstream CXXC5 and downstream PGC-1α [ 39 ]. In addition, CXXC5 and PGC-1α can further modulate p53 activation, which is responsible for cell-cycle arrest and apoptosis, respectively [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

CXXC5 mitigates P. gingivalis-inhibited cementogenesis by influencing mitochondrial biogenesis

Ma,

Wang,

Huang

et al. 2024

Cell Commun Signal

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Background Cementoblasts on the tooth-root surface are responsible for cementum formation (cementogenesis) and sensitive to Porphyromonas gingivalis stimulation. We have previously proved transcription factor CXXC-type zinc finger protein 5 (CXXC5) participates in cementogenesis. Here, we aimed to elucidate the mechanism in which CXXC5 regulates P. gingivalis-inhibited cementogenesis from the perspective of mitochondrial biogenesis. Methods In vivo, periapical lesions were induced in mouse mandibular first molars by pulp exposure, and P. gingivalis was applied into the root canals. In vitro, a cementoblast cell line (OCCM-30) was induced cementogenesis and submitted for RNA sequencing. These cells were co-cultured with P. gingivalis and examined for osteogenic ability and mitochondrial biogenesis. Cells with stable CXXC5 overexpression were constructed by lentivirus transduction, and PGC-1α (central inducer of mitochondrial biogenesis) was down-regulated by siRNA transfection. Results Periapical lesions were enlarged, and PGC-1α expression was reduced by P. gingivalis treatment. Upon apical inflammation, Cxxc5 expression decreased with Il-6 upregulation. RNA sequencing showed enhanced expression of osteogenic markers, Cxxc5, and mitochondrial biogenesis markers during cementogenesis. P. gingivalis suppressed osteogenic capacities, mitochondrial biogenesis markers, mitochondrial (mt)DNA copy number, and cellular ATP content of cementoblasts, whereas CXXC5 overexpression rescued these effects. PGC-1α knockdown dramatically impaired cementoblast differentiation, confirming the role of mitochondrial biogenesis on cementogenesis. Conclusions CXXC5 is a P. gingivalis-sensitive transcription factor that positively regulates cementogenesis by influencing PGC-1α-dependent mitochondrial biogenesis.

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“…PI3K-AKT signaling pathway could mediate hypoxia-induced fibroblast activation, collagen synthesis, and EMT regulation leading to renal fibrosis [ 91 ]. Several studies have confirmed that inhibition of the PI3K/AKT signaling pathway can alleviate renal interstitial fibrosis [ 99 – 101 ]. These results suggest that the PI3K/AKT signaling pathway crosstalk with the TGF- β signaling pathway plays a pivotal role in the progression of tumors and renal interstitial fibrosis.…”

Section: Cda1 and Renal Fibrosis In Dnmentioning

confidence: 99%

The Role of Cell Division Autoantigen 1 (CDA1) in Renal Fibrosis of Diabetic Nephropathy

Chen

et al. 2021

BioMed Research International

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The common kidney disease diabetic nephropathy (DN) accounts for significant morbidity and mortality in patients with diabetes, and its effective diagnosis in incipient stages is still lacking. Renal fibrosis is the main pathological feature of DN. Cell division autoantigen 1 (CDA1), a phosphorylated protein encoded by TSPYL2 on the X chromosome, plays a fibrogenic role by modulating the transforming growth factor-β (TGF-β) signaling, but the exact mechanism remains unclear. TGF-β signaling has been recognized as the key factor in promoting the development and progression of DN. At present, strict control of blood sugar and blood pressure can significantly lower the development and progression of DN in the early stages, and many studies have shown that blocking TGF-β signaling can delay the progress of DN. However, TGF-β is a multifunctional cytokine. Its direct intervention may result in increased side effects. Therefore, the targeted intervention of CDA1 not only can block the TGF-β signaling pathway but also can reduce these side effects. In this article, we review the main physiological roles of CDA1, with particular attention to its effect and potential mechanism in the renal fibrosis of DN.

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Antifibrotic role of PGC-1α-siRNA against TGF-β1-induced renal interstitial fibrosis

Cited by 15 publications

References 52 publications

Signaling Pathways Involved in Diabetic Renal Fibrosis

Signaling Pathways Involved in Diabetic Renal Fibrosis

CXXC5 mitigates P. gingivalis-inhibited cementogenesis by influencing mitochondrial biogenesis

The Role of Cell Division Autoantigen 1 (CDA1) in Renal Fibrosis of Diabetic Nephropathy

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