TWIST1 transcriptionally upregulates complement 3 in glomerular mesangial cells from spontaneously hypertensive rats

Otsuki, Tomoyasu; Fukuda, Noboru; Cui, Lan; Ueno, Takayoshi; Otsuki, Masari; Abe, Masanori

doi:10.1038/s41440-021-00750-x

Cited by 2 publications

(3 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We recently investigated the role of TWIST1 in the increased expression of C3 in MCs from SHR. TWIST1 siRNA significantly decreased the expression of C3 mRNA in MCs from SHR, indicating that TWIST1 upregulates the C3 gene in MCs from SHR [10]. In the present experiments, to evaluate the involvement of TWIST1 as a transcription factor in upregulation of the…”

Section: Discussionmentioning

confidence: 81%

See 1 more Smart Citation

Twist-related protein 1 induces epithelial-mesenchymal transition and renal fibrosis through the upregulation of complement 3

Otsuki

Fukuda

Chen³

et al. 2022

PLoS ONE

Self Cite

View full text Add to dashboard Cite

We have demonstrated that complement 3 (C3) is upregulated and induces epithelial-mesenchymal transition (EMT) phenomenon and renal fibrosis in unilateral ureteral obstruction (UUO) kidney. We investigated roles of twist-related protein 1 (TWIST1) in EMT phenomenon and renal fibrosis through C3 upregulation in a mouse UUO model with gene silencer pyrrole-imidazole (PI) polyamides targeting TWIST1. We designed and synthesized PI polyamides targeting TWIST1 binding site on mouse pre-pro C3 promoter. Increased expression C3 mRNA with interferon-γ was significantly inhibited with PI polyamide in nephrotubular epithelial cells. Immunofluorescence showed suppression of E-cadherin and enhancement of α-smooth muscle actin (α-SMA) stainings as EMT phenomena in UUO kidney. TWIST1 and C3 expression was significantly increased in UUO kidney versus contralateral unobstructed kidney (CUK). Expression of transforming growth factor-β1 (TGF-β1), α-SMA and renin mRNAs was increased in UUO kidney versus CUK. Systemic administration of TWIST1 PI polyamide significantly suppressed increased C3 expression in UUO kidney versus CUK. PI polyamide administration also suppressed the increased expression of TGF-β1, α-SMA and renin mRNAs and histologically improved renal fibrosis in UUO kidney. These findings indicate that TWIST1 induces EMT phenomenon and renal fibrosis by TGF-β1 upregulation of C3 in mouse UUO model and that TWIST1 PI polyamide may be a novel medicine for renal fibrosis.

show abstract

Section: Discussionmentioning

confidence: 81%

“…We recently found that the expression of TWIST1 is enhanced in SHR-derived renal mesangial cells (MCs) and that the increased TWIST1 is involved in the upregulation of C3 in SHR. It is possible that TWIST1 is also involved in the EMT phenomenon to induce renal fibrosis [10].…”

Section: Introductionmentioning

confidence: 99%

Twist-related protein 1 induces epithelial-mesenchymal transition and renal fibrosis through the upregulation of complement 3

Otsuki

Fukuda

Chen³

et al. 2022

PLoS ONE

Self Cite

View full text Add to dashboard Cite

show abstract

“…Fukuda and his colleagues have shown that complement 3 (C3) is a primary factor that activates intrarenal RAS [Supplementary Information 12 - 1 , 2 ]. Otsuki and Fukuda et al additionally demonstrated that TWIST1, a transcription factor that regulates mesodermal embryogenesis, transcriptionally upregulates C3 in glomerular mesangial cells from SHRs [ 201 ].…”

Section: Basic Research: Elucidation Of the “Mosaic” Pathogenesis Of ...mentioning

confidence: 99%

Update on Hypertension Research in 2021

et al. 2022

View full text Add to dashboard Cite

show abstract

TWIST1 transcriptionally upregulates complement 3 in glomerular mesangial cells from spontaneously hypertensive rats

Cited by 2 publications

References 21 publications

Twist-related protein 1 induces epithelial-mesenchymal transition and renal fibrosis through the upregulation of complement 3

Twist-related protein 1 induces epithelial-mesenchymal transition and renal fibrosis through the upregulation of complement 3

Update on Hypertension Research in 2021

Contact Info

Product

Resources

About