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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

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      About Blood Purification: 3.0 Impact Factor I 5.6 CiteScore I 0.83 Scimago Journal & Country Rank (SJR)

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      Expression of SM22α (transgelin) in glomerular and interstitial renal injury.

      Nephron. Experimental Nephrology
      Animals, Epithelial Cells, metabolism, pathology, Immunohistochemistry, Kidney, ultrastructure, Kidney Diseases, etiology, Kidney Glomerulus, surgery, Male, Microfilament Proteins, biosynthesis, Microscopy, Immunoelectron, Muscle Proteins, Nephrectomy, Nephrosis, chemically induced, Puromycin Aminonucleoside, Rats, Rats, Inbred WKY, Rats, Sprague-Dawley, Reperfusion Injury, complications, Time Factors

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          Abstract

          SM22α, transgelin, is abundantly expressed in smooth muscle tissues and our previous work demonstrated that it is a novel marker of injured glomerular epithelial cells in rat antiglomerular basement membrane nephritis. In this study, we investigated SM22α expression in models of glomerular and interstitial renal injury. The 5/6 nephrectomy (Nx) model, ischemia-reperfusion (I/R) model and puromycin aminonucleoside (PAN) nephrosis of rats were studied. Immunohistochemical analyses and immunoelectron microscopic studies of SM22α expression were performed. In the 5/6 Nx model, SM22α was first expressed in peritubular interstitial cells and was also expressed in injured glomerular epithelial cells at 8 weeks. In the I/R model, SM22α expression was induced in peritubular interstitial cells as early as 12 h after I/R with expression sustained at 7 days. However, SM22α was not detected in any glomerular cells or tubular epithelial cells. In PAN nephrosis, SM22α was only expressed in glomerular epithelial cells after 1 week, but expression was transient. SM22α was expressed in glomerular epithelial cells and interstitial cells in renal injury. SM22α is differentially upregulated in various models of renal injury and merits further study. Copyright © 2010 S. Karger AG, Basel.

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          Transgelin: an actin-binding protein and tumour suppressor.

          Transgelin is a shape change sensitive 22 kDa actin-binding protein of the calponin family. It contains a C-terminal calponin-like module (CLIK(23)) and an upstream positively charged amino acid region required for actin binding. Transgelin is ubiquitous to vascular and visceral smooth muscle and is an early marker of smooth muscle differentiation, where its expression is driven by CArG box, smooth muscle gene promoter. It is also present in fibroblasts, and some epithelium where expression is likely driven by TGF-beta1. Transgelin null mice reveal that, whilst it is not required for smooth muscle development, transgelin may be involved in calcium-independent smooth muscle contraction. Recent evidence suggests that transgelin acts as a tumour suppressor. Its expression is lost in prostate, breast and colon cancers. This is consistent with suppression of the metallo matrix protease-9 (MMP-9) by transgelin, where MMP-9 is upregulated in these common cancers.
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            TGF-  Signaling in Renal Disease

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              Transgelin is a direct target of TGF-beta/Smad3-dependent epithelial cell migration in lung fibrosis.

              Enhanced transforming growth factor (TGF) -beta signaling contributes to idiopathic pulmonary fibrosis (IPF), a progressive and fatal disease characterized by alveolar epithelial type II (ATII) cell hyperplasia, (myo)fibroblast accumulation, and excessive extracellular matrix deposition. TGF-beta is a potent inducer of lung fibrosis, and it regulates the ATII cell phenotype; however, direct TGF-beta target genes controlling the ATII cell phenotype remain elusive. Here, we identified the transgelin (tagln) gene as a novel immediate target of TGF-beta/Smad3-dependent gene expression in ATII cells using a Smad3 chromatin immunoprecipitation (ChIP) screen. Direct ChIP confirmed the rapid and specific binding of Smad3 to the tagln promoter. Luciferase assays demonstrated transactivation of the tagln promoter by activin-like kinase (Alk) 5-mediated TGF-beta signaling. TGF-beta treatment resulted in rapid up-regulation of tagln, but not tagln2, mRNA and protein expression, assessed by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence. In vivo, tagln expression was significantly increased in ATII cells of mice during bleomycin-induced lung fibrosis, as well as in lung specimen obtained from IPF patients, as assessed by RT-PCR and immunohistochemistry. Knockdown of tagln using siRNA inhibited TGF-beta-induced migration of lung epithelial A549 cells, as well as primary ATII cells. We thus identified tagln as a novel target of TGF-beta/Smad3-dependent gene expression in ATII cells. Increased ATII cell expression of tagln in experimental and idiopathic pulmonary fibrosis may contribute to TGF-beta-dependent ATII cell injury, repair, and migration in lung fibrosis.
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