Serum response factor provokes epithelial-mesenchymal transition in renal tubular epithelial cells of diabetic nephropathy

Zhao, Liang; Chi, Lingzhen; Zhao, Jun; Wang, Xueling; Chen, Zhuo; Meng, Linghang; Liu, Gang; Guan, Guangju; Wang, Fei

doi:10.1152/physiolgenomics.00058.2016

Cited by 26 publications

(21 citation statements)

References 30 publications

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“…He et al (35) demonstrated that SRF promotes EMT in human peritoneal mesothelial cells. SRF also provokes EMT in renal tubular epithelial cells of diabetic nephropathy (36), and it induces EMT in hepatocellular carcinoma, prostate cancer, and gastric cancer (37). Therefore, SRF has a significant role in EMT and cancer metastasis.…”

Section: Discussionmentioning

confidence: 99%

Suppressing serum response factor inhibits invasion in cervical cancer cell lines via regulating Egr‑1 and epithelial-mesenchymal transition

2018

Int J Mol Med

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Section: Discussionmentioning

confidence: 99%

Suppressing serum response factor inhibits invasion in cervical cancer cell lines via regulating Egr‑1 and epithelial-mesenchymal transition

2018

Int J Mol Med

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“…Although in vitro studies support the existence of EMT, evidence that fibroblasts derive from epithelial cells in vivo is controversial (44,45). However, recently Zhao et al (46) have reported both in vitro in tubular cells after high glucose treatment and in vivo in diabetic rats, the increase in mesenchymal markers (fibronectin, collagen-1, a-SMA, and fibroblast-specific protein-1) and the decrease in epithelial markers (E-cadherin and zonula occludens-1), thus concluding that HG plays an important role in EMT and in DN dysfunction. In addition, cytoskeletal alterations have been described to play an important role in EMT in breast cancer cells (47).…”

Section: Discussionmentioning

confidence: 99%

Lysine 63 ubiquitination is involved in the progression of tubular damage in diabetic nephropathy

Pontrelli¹,

Conserva

Papale

et al. 2016

FASEB j.

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The purpose of our study was to evaluate how hyperglycemia (HG) influences Lys63 protein ubiquitination and its involvement in tubular damage and fibrosis in diabetic nephropathy (DN). Gene and protein expression of UBE2v1, a ubiquitin-conjugating E2-enzyme variant that mediates Lys63-linked ubiquitination, and Lys63-ubiquitinated proteins increased in HK2 tubular cells under HG. Matrix-assisted laser desorption/ionization-time of flight/tandem mass spectrometry identified 30 Lys63-ubiquitinated proteins, mainly involved in cellular organization, such as β-actin, whose Lys63 ubiquitination increased under HG, leading to cytoskeleton disorganization. This effect was reversed by the inhibitor of the Ubc13/UBE2v1 complex NSC697923. Western blot analysis confirmed that UBE2v1 silencing in HK2 under HG, restored Lys63-β-actin ubiquitination levels to the basal condition. Immunohistochemistry on patients with type 2 diabetic (T2D) revealed an increase in UBE2v1- and Lys63-ubiquitinated proteins, particularly in kidneys of patients with DN compared with control kidneys and other nondiabetic renal diseases, such as membranous nephropathy. Increased Lys63 ubiquitination both in vivo in patients with DN and in vitro, correlated with α-SMA expression, whereas UBE2v1 silencing reduced HG-induced α-SMA protein levels, returning them to basal expression. In conclusion, UBE2v1- and Lys63-ubiquitinated proteins increase in vitro under HG, as well as in vivo in T2D, is augmented in patients with DN, and may affect cytoskeleton organization and influence epithelial-to-mesenchymal transition. This process may drive the progression of tubular damage and interstitial fibrosis in patients with DN.-Pontrelli, P., Conserva, F., Papale, M., Oranger, A., Barozzino, M., Vocino, G., Rochetti, M. T., Gigante, M., Castellano, G., Rossini, M., Simone, S., Laviola, L., Giorgino, F., Grandaliano, G., Di Paolo, S., Gesualdo, L. Lysine 63 ubiquitination is involved in the progression of tubular damage in diabetic nephropathy.

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“…This is a synthetic compound originally identified as an inhibitor of the small GTPase RhoA 174 , but nowadays accepted as an inhibitor of SRF-dependent responses 175–178 . SRF is a transcription factor considered as a master regulator in both cancer and embryonic development 179 .…”

Section: Micalmentioning

confidence: 99%

Regulated methionine oxidation by monooxygenases

Manta

Gladyshev

2017

Free Radical Biology and Medicine

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Protein function can be regulated via post-translational modifications by numerous enzymatic and non-enzymatic mechanisms, including oxidation of cysteine and methionine residues. Redox-dependent regulatory mechanisms have been identified for nearly every cellular process, but the major paradigm has been that cellular components are oxidized (damaged) by reactive oxygen species (ROS) in a relatively unspecific way, and then reduced (repaired) by designated reductases. While this scheme may work with cysteine, it cannot be ascribed to other residues, such as methionine, whose reaction with ROS is too slow to be biologically relevant. However, methionine is clearly oxidized in vivo and enzymes for its stereoselective reduction are present in all three domains of life. Here, we revisit the chemistry and biology of methionine oxidation, with emphasis on its generation by enzymes from the monooxygenase family. Particular attention is placed on MICALs, a recently discovered family of proteins that harbor an unusual flavin-monooxygenase domain with an NADPH-dependent methionine sulfoxidase activity. Based on the structural and kinetic information we provide a rational framework to explain MICAL mechanism, inhibition, and regulation. Methionine residues that are targeted by MICALs are reduced back by methionine sulfoxide reductases, suggesting that reversible methionine oxidation may be a general mechanism analogous to the regulation by phosphorylation by kinases/phosphatases. The identification of new enzymes that catalyze the oxidation of methionine will open a new area of research at the forefront of redox signaling.

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Serum response factor provokes epithelial-mesenchymal transition in renal tubular epithelial cells of diabetic nephropathy

Cited by 26 publications

References 30 publications

Suppressing serum response factor inhibits invasion in cervical cancer cell lines via regulating Egr‑1 and epithelial-mesenchymal transition

Suppressing serum response factor inhibits invasion in cervical cancer cell lines via regulating Egr‑1 and epithelial-mesenchymal transition

Lysine 63 ubiquitination is involved in the progression of tubular damage in diabetic nephropathy

Regulated methionine oxidation by monooxygenases

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