Transgelin Up-Regulation in Obstructive Nephropathy

Abstract

Fibrosis is a complex and multifactorial process, affecting the structure and compromising the function of several organs. Among those, renal fibrosis is an important pathological change, eventually leading to renal failure. Proteomic analysis of the renal parenchyma in the well-established rat model of unilateral ureteral obstruction (UUO model) suggested that transgelin was up-regulated during the development of fibrosis. Transgelin up-regulation was confirmed both at the protein and at the mRNA level. It was observed that at early stages of fibrosis transgelin was mainly expressed in the interstitial compartment and, more specifically, in cells surrounding the glomeruli. Subsequently, it was confirmed that transgelin expressing cells were activated fibroblasts, based on their extensive co-expression of α-SMA and their complete lack of co-distribution with markers of other cell types (endothelial, epithelial and cells of the immune system). These periglomerular fibroblasts exhibited staining for transgelin mainly cytoplasmic but occasionally nuclear as well. In addition, transgelin expression in periglomerular fibroblasts was absent in renal fibrosis developed in a hypertensive model, compared to the UUO model. Promoter analysis indicated that there are several conserved motifs for transcription factor binding. Among those, Kruppel-like factor 6 was found to be up-regulated in transgelin positive periglomerular activated fibroblasts, suggesting a possible involvement in the mechanism of transgelin up-regulation. These data strongly suggest that transgelin is up-regulated in the obstructive nephropathy and could be used as a novel marker for renal fibrosis in the future.

Whole-transcriptome analysis of UUO mouse model of renal fibrosis reveals new molecular players in kidney diseases

“…1B ; Supplemental Fig. 1 and data not shown 9 ). Libraries were sequenced, low-quality reads and rRNA sequences were filtered, total clean reads were mapped to genome and mapped reads were assembled into putative transcripts ( Supplemental Table 1 ).…”

The transition of smooth muscle cells from a contractile to a migratory, phagocytic phenotype: direct demonstration of phenotypic modulation

“…A difficulty in unequivocally identifying the cells underlying plaque formation, and those cells studied in culture assumed to be SMCs, is ambiguity in the markers used to identify cells. Markers associated with SM may also be found in several other cell types (Shapland et al 1988;Arciniegas et al 1992;Basson et al 1992;Moroianu et al 1993;Sartore et al 2001;Martin et al 2009;Ludin et al 2012;Shen et al 2012;Karagianni et al 2013).…”

“…Instead, SMA and SM22α are probably the most widely used markers of the proliferative/migratory SM phenotype. However, SMA and SM22α are also expressed in many other non-SMCs including endothelial cells (ECs), fibroblasts, monocytes and macrophage (Shapland et al 1988;Arciniegas et al 1992;Basson et al 1992;Moroianu et al 1993;Sartore et al 2001;Martin et al 2009;Ludin et al 2012;Shen et al 2012;Karagianni et al 2013), raising significant uncertainties over cell sources.…”

Intrarenal B Cell Cytokines Promote Transplant Fibrosis and Tubular Atrophy

“…Other mechanisms promoting fibrosis were, therefore, examined: activated pericytes express platelet derived growth factor receptor‐β (PDGFR‐β) and can differentiate into fibroblasts . Transgelin is an actin stress fiber‐associated protein and an early marker of smooth muscle cell differentiation, and is associated with renal fibroblast activation . Both transgelin and PDGFR‐β, which may be alternative markers of fibroblast activation, were expressed in areas of tubular atrophy and we speculate that B cells could potentially drive fibrocyte or fibroblast activation through these mechanisms.…”