Gcm1 is involved in cell proliferation and fibrosis during kidney regeneration after ischemia–reperfusion injury

Kamejima, Sahoko; Tatsumi, Norifumi; Anraku, Akane; Suzuki, Hideaki; Ohkido, Ichiro; Yokoo, Takashi; Okabe, Masataka

doi:10.1038/s41598-019-44161-y

Cited by 11 publications

(9 citation statements)

References 63 publications

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“…Both macrophage phenotypes promote kidney fibrosis [ 9 ]. M1 macrophages can cause local tissue damage by inducing the apoptosis of the surrounding cells and releasing proinflammatory substances such as tumor necrosis factor (TNF)-α and large amounts of nitric oxide (NO) through the inducible NO synthase (iNOS) [ 10 , 11 ]. These proinflammatory factors promote fibrosis through inhibited degradation of fibrinogen by the inhibition of matrix metalloproteinases [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Twist1 regulates macrophage plasticity to promote renal fibrosis through galectin-3

Sun

Wei

et al. 2022

Cell. Mol. Life Sci.

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Renal interstitial fibrosis is the pathological basis of end-stage renal disease, in which the heterogeneity of macrophages in renal microenvironment plays an important role. However, the molecular mechanisms of macrophage plasticity during renal fibrosis progression remain unclear. In this study, we found for the first time that increased expression of Twist1 in macrophages was significantly associated with the severity of renal fibrosis in IgA nephropathy patients and mice with unilateral ureteral obstruction (UUO). Ablation of Twist1 in macrophages markedly alleviated renal tubular injury and renal fibrosis in UUO mice, accompanied by a lower extent of macrophage infiltration and M2 polarization in the kidney. The knockdown of Twist1 inhibited the chemotaxis and migration of macrophages, at least partially, through the CCL2/CCR2 axis. Twist1 downregulation inhibited M2 macrophage polarization and reduced the secretion of the profibrotic factors Arg-1, MR (CD206), IL-10, and TGF-β. Galectin-3 was decreased in the macrophages of the conditional Twist1-deficient mice, and Twist1 was shown to directly activate galectin-3 transcription. Up-regulation of galectin-3 recovered Twist1-mediated M2 macrophage polarization. In conclusion, Twist1/galectin-3 signaling regulates macrophage plasticity (M2 phenotype) and promotes renal fibrosis. This study could suggest new strategies for delaying kidney fibrosis in patients with chronic kidney disease.

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Section: Introductionmentioning

confidence: 99%

Twist1 regulates macrophage plasticity to promote renal fibrosis through galectin-3

Sun

Wei

et al. 2022

Cell. Mol. Life Sci.

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“…That was indicated by the cell’s density being higher compared to negative control with cells density of 70–80% confluence. The previous studies showed that TGF-β1 could induce fibroblast proliferation ( Kamejima et al, 2019 ; Prahastuti et al, 2019 ). The results of this study proved that quercetin was able to inhibit the cells proliferation of CKD cells model by reducing the TGF-β1 level.…”

Section: Discussionmentioning

confidence: 99%

Quercetin prevents chronic kidney disease on mesangial cells model by regulating inflammation, oxidative stress, and TGF-β1/SMADs pathway

Widowati

Prahastuti

Tjokropranoto

et al. 2022

PeerJ

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Background Chronic kidney disease (CKD) happens due to decreasing kidney function. Inflammation and oxidative stress have been shown to result in the progression of CKD. Quercetin is widely known to have various bioactivities including antioxidant, anticancer, and anti-inflammatory activities. Objective To evaluate the activity of quercetin to inhibit inflammation, stress oxidative, and fibrosis on CKD cells model (mouse mesangial cells induced by glucose). Methods and Material The SV40 MES 13 cells were plated in a 6-well plate with cell density at 5,000 cells/well. The medium had been substituted for 3 days with a glucose-induced medium with a concentration of 20 mM. Quercetin was added with 50, 10, and 5 µg/mL concentrations. The negative control was the untreated cell. The levels of TGF-β1, TNF-α, and MDA were determined using ELISA KIT. The gene expressions of the SMAD7, SMAD3, SMAD2, and SMAD4 were analyzed using qRT-PCR. Results Glucose can lead to an increase in inflammatory cytokines TNF-α, TGF-β1, MDA as well as the expressions of the SMAD2, SMAD3, SMAD4, and a decrease in SMAD7. Quercetin caused the reduction of TNF-α, TGF-β1, MDA as well as the expression of the SMAD2, SMAD3, SMAD4, and increased SMAD7. Conclusion Quercetin has anti-inflammation, antioxidant, antifibrosis activity in the CKD cells model. Thus, quercetin is a promising substance for CKD therapy and further research is needed to prove this in CKD animal model.

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“…3h). The destruction of renal tubular epithelial cells caused by I/R secondarily causes interstitial fibrosis of the renal parenchyma and rapidly reduces renal function 36 . Fibronectin deposition and TGF-b1 were analyzed to determine whether LPA treatment had any effect on the development and progression of fibrosis during IRI.…”

Section: Effect Of Lpa Treatment On Renal Histopathology and Fibrosis After I/rmentioning

confidence: 99%

“…LPA receptors expressed in the kidney (LPA 1 R, LPA 2 R and LPA 3 R) are coupled to a great variety of G proteins subsets that activate cell signaling cascades. Both the Gα q/11 sub-unit and the βγ sub-unit from G i/0 , dissociated from the trimeric conformation, modulate the PLC/PKC signaling pathway that is known to regulate the Na + transporters 15,31,36 . We measured PKC activity in the renal cortex of all experimental groups.…”

Section: Effect Of Lpa Treatment On Tubular Na+ Handling: the Influence On The Active Na + Transportersmentioning

confidence: 99%

Lysophosphatidic Acid Prevents Ischemia Reperfusion Injury but does not Prevent Tubular Dysfunction

Gonsalez¹,

Cortes²,

Romanelli³

et al. 2020

J Nephrol Sci

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Lysophosphatidic acid (LPA) protects the kidneys from tissue ischemic reperfusion injury (IRI), but its impact on renal function is primarily limited to glomerular function. We estimated the status of renal function by a complete glomerular and tubular functional analysis to test the hypothesis that LPA treatment during ischemia-reperfusion (I/R) protects renal function by attenuating IRI. Male Wistar rats were subjected to bilateral kidney I/R. Along with ischemia, LPA was administered. LPA increased levels of plasma LPA, downregulated LPA2R, prevented interstitial fibronectin and TGF-β1 accumulation, and prevented a decrease in glomerular filtration rate (GFR). I/R increased urine volume and proteinuria and decreased fractional Na+ excretion (FENa) and urine osmolality. These effects were not prevented by LPA. The reduction in FENa was attributed to disruption in tubular Na+ transport and downregulation of protein kinase C (PKC) activity. LPA treatment maintained (Na++K+)ATPase activity to the control level, due to a sustained sensitivity to PLC/PKC pathway. Na+-ATPase activity was insensitivity to LPA treatment. This ineffectiveness was associated with downregulation of LPA2R, resulting in low FENa. Altogether, LPA treatment maintained normal kidney structure and prevented the reduction of glomerular function. However, even in the setting of preserved GFR, impaired tubular function may present a high risk for silent progression of kidney disease.

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Gcm1 is involved in cell proliferation and fibrosis during kidney regeneration after ischemia–reperfusion injury

Cited by 11 publications

References 63 publications

Twist1 regulates macrophage plasticity to promote renal fibrosis through galectin-3

Twist1 regulates macrophage plasticity to promote renal fibrosis through galectin-3

Quercetin prevents chronic kidney disease on mesangial cells model by regulating inflammation, oxidative stress, and TGF-β1/SMADs pathway

Lysophosphatidic Acid Prevents Ischemia Reperfusion Injury but does not Prevent Tubular Dysfunction

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