Transglutaminase-1 Regulates Renal Epithelial Cell Proliferation through Activation of Stat-3

Zhang, Zhu; Xing, Jingping; Ma, Li; Gong, Rujun; Chin, Y. Eugene; Zhuang, Songlin

doi:10.1074/jbc.m808396200

Cited by 19 publications

(18 citation statements)

References 43 publications

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“…It also regulates the survival and proliferation of renal epithelial cells, essential processes for renal regeneration [Ponnusamy et al, 2009;Zhang et al, 2009]. Consistent with these reports, we observed strong TGase-1 expression in both residual and newly recruited vocal fold epithelial cells postinjury.…”

Section: Discussionsupporting

confidence: 79%

E-Cadherin and Transglutaminase-1 Epithelial Barrier Restoration Precedes Type IV Collagen Basement Membrane Reconstruction following Vocal Fold Mucosal Injury

Ling

Raasch

Welham

2010

Cells Tissues Organs

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The vocal fold epithelium is critical to upper airway immunologic defense and water/ion transport; therefore, any form of physical trauma or insult increases the vulnerability of this structure to functional impairment and pathogen invasion/infection. In this study, we examined the reestablishment of epithelial and basement membrane barrier structures in a well-established rat model of vocal fold mucosal injury. We observed active cell recruitment culminating in peak hyperplasia at 3 days postinjury, the establishment of robust E-cadherin+ and transglutaminase-1+ biochemical barrier signals along the epithelial surface by 3 days postinjury, and the persistent absence of a type IV collagen+ basement membrane at 7 days postinjury. The distinct spatial and temporal immunoactivity of these molecules is consistent with a programmed repair process driving the restoration of vocal fold mucosal integrity and permeability. These data may inform future efforts to optimize functional mucosal recovery postinjury and avoid undesirable events such as barrier compromise or epithelial metaplasia.

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Section: Discussionsupporting

confidence: 79%

E-Cadherin and Transglutaminase-1 Epithelial Barrier Restoration Precedes Type IV Collagen Basement Membrane Reconstruction following Vocal Fold Mucosal Injury

Ling

Raasch

Welham

2010

Cells Tissues Organs

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“…OSM treatment induced pSTAT1/3, expression of cyclin D1 and -E and cellular proliferation ( Figure 6). Consistent with these findings phosphorylated STAT3 was shown to induce proliferation in RPTCs 28 and renal cancer cells. 29 Arakawa et al 30 have shown that pSTAT3 is correlated with cell proliferation in human glomerulonephritis.…”

Section: Socs-3 In Chronic Kidney Disease H Neuwirt Et Alsupporting

confidence: 75%

“…29 Arakawa et al 30 have shown that pSTAT3 is correlated with cell proliferation in human glomerulonephritis. Zhang et al 28 have published recently that pSTAT3-induced proliferation in renal proximal tubule cells. Consistent with our results this effect was mediated by upregulation of cyclin D1 and E.…”

Section: Socs-3 In Chronic Kidney Disease H Neuwirt Et Almentioning

confidence: 99%

“…25 Moreover, activated STAT3 was shown to be implicated in 3D tubule formation (¼ epithelial differentiation) in renal proximal tubule cells (RPTCs). 26,27 Additionally, various studies showed that STAT3 also induced proliferation in renal cells [28][29][30] by upregulation of cyclin D1 and -E. 28 Regulators of STAT signaling are the phosphatase SHP-1, protein inhibitors of activated STAT (PIAS) and suppressors of cytokine signaling (SOCS) proteins. [31][32][33][34][35] The SOCS family consists of eight molecules (cytokine inducible SH2-containing protein CIS and SOCS-1-7), which contain a variable amino-terminal region, a central SH2 domain, a conserved carboxy-terminal SOCS box and in case of SOCS-1 and -3 a kinase inhibitory region.…”

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confidence: 99%

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SOCS-3 is downregulated in progressive CKD patients and regulates proliferation in human renal proximal tubule cells in a STAT1/3 independent manner

Neuwirt

Eder

Puhr

et al. 2013

Laboratory Investigation

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Proliferation and the sequence of epithelial to mesenchymal transition (EMT) and mesenchymal to epithelial transition (MET), called epithelial-mesenchymal-epithelial (EME) cycling are pivotal mechanisms of kidney repair and fibrosis. Furthermore, data suggest that dedifferentiation (EMT) is a prerequisite for proliferation of tubule cells. These processes have been shown to be regulated by STAT1/3 signaling. Suppressor of cytokine signaling-3 (SOCS-3) is a negative regulator of STAT1/3 signaling. Using a transcriptomics data set of patients with proteinuric kidney diseases we found that low levels of SOCS-3 RNA were associated with high-serum creatinine values in the long-term follow-up, which suggested a role of SOCS-3, regulated signaling in progression of chronic kidney disease. This result was validated in an independent cohort of patients with proteinuric nephropathies on protein level. In addition B60% of STAT target genes were differentially expressed in relation to stable kidney disease patients. Using two renal cellular models and SOCS-3 knockdown by short interfering RNA we investigated SOCS-3 effects on oncostatin M-induced STAT activation, differentiation and proliferation. SOCS-3 knockdown resulted in enhanced pSTAT1/3 phosphorylation and epithelial differentiation. The latter effect was only slightly enhanced by OSM treatment. Cellular proliferation was inhibited after SOCS-3 knockdown. This effect could not be further stimulated by OSM. Effects of SOCS-3 knockdown were not enhanced by downregulation of STAT1/3, suggesting a STAT independent effect on cell cycle regulators. Indeed, knockdown and overexpression of SOCS-3 were associated with decrease and increase of cyclin D1, -E and proliferation, respectively. In summary, SOCS-3 inhibits phosphorylation of pSTAT1/3 in renal tubule cells. Additionally, we show for the first time that-in vivo-loss of SOCS-3 is associated with unfavorable prognosis. In vitro, downregulation of SOCS-3 inhibits dedifferentiation (EMT) and cellular proliferation in kidney proximal tubule cells.

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“…It has been recently described that TG1 protects renal epithelial cells from apoptosis and also promotes proliferation by modulating signaling molecules such as Stat-3 and AKT [6,7]. TG2 is involved in renal diseases, such as fibrosis and IgA nephropathy, resulting in modification of extracellular matrix and immunoglobulin (IgA) receptors, respectively [8,9].…”

Section: Introductionmentioning

confidence: 99%

Early response as shown by enhancement of transglutaminase 1 expression after cisplatin-induced acute kidney injury

Furukawa

Yamane

Tatsukawa

et al. 2015

Archives of Biochemistry and Biophysics

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Transglutaminase-1 Regulates Renal Epithelial Cell Proliferation through Activation of Stat-3

Cited by 19 publications

References 43 publications

E-Cadherin and Transglutaminase-1 Epithelial Barrier Restoration Precedes Type IV Collagen Basement Membrane Reconstruction following Vocal Fold Mucosal Injury

E-Cadherin and Transglutaminase-1 Epithelial Barrier Restoration Precedes Type IV Collagen Basement Membrane Reconstruction following Vocal Fold Mucosal Injury

SOCS-3 is downregulated in progressive CKD patients and regulates proliferation in human renal proximal tubule cells in a STAT1/3 independent manner

Early response as shown by enhancement of transglutaminase 1 expression after cisplatin-induced acute kidney injury

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