Abstract:Mesangial cell (MC) migration is essential during glomerular repair and kidney development. The aim of the study was to identify marker/player for glomerular progenitor/reserve cells migrating into the glomerulus after MC injury and during glomerulogenesis in the rat. Experimental mesangial proliferative nephritis was induced in Sprague Dawley rats by intravenous injection of OX-7 antibody. We investigated mRNA expression profiles in isolated glomeruli from on days 0, 1, 2, 3, and 5 after induction of anti-Thy… Show more
“…Desmin is an intermediate filament protein that has also previously been found to be upregulated in podocytes of the non-clipped kidney 2K1C hypertensive rats [50] and is suggested as a marker for glomerular injury in puromycin aminonucleoside nephrosis [51] and diabetic nephropathy [52] in rat models. Transgelin is upregulated in podocytes of several nephropathies [53, 54] and has been reported as markers for repopulating mesangial cells in response to damage [55]. The former was also suggested by our immunohistochemistry findings.…”
BackgroundIt is well known that hypertension may cause glomerular damage, but the molecular mechanisms involved are still incompletely understood.MethodsIn the present study, we used formalin-fixed paraffin-embedded (FFPE) tissue to investigate changes in the glomerular proteome in the non-clipped kidney of two-kidney one-clip (2K1C) hypertensive rats, with special emphasis on the glomerular filtration barrier. 2K1C hypertension was induced in 6-week-old Wistar Hannover rats (n = 6) that were sacrificed 23 weeks later and compared with age-matched sham-operated controls (n = 6). Tissue was stored in FFPE tissue blocks and later prepared on tissue slides for laser microdissection. Glomeruli without severe morphological damage were isolated, and the proteomes were analysed using liquid chromatography–tandem mass spectrometry.Results2K1C glomeruli showed reduced abundance of proteins important for slit diaphragm complex, such as nephrin, podocin and neph1. The podocyte foot process had a pattern of reduced abundance of transmembrane proteins but unchanged abundances of the podocyte cytoskeletal proteins synaptopodin and α-actinin-4. Lower abundance of important glomerular basement membrane proteins was seen. Possible glomerular markers of damage with increased abundance in 2K1C were transgelin, desmin and acyl-coenzyme A thioesterase 1.ConclusionsMicrodissection and tandem mass spectrometry could be used to investigate the proteome of isolated glomeruli from FFPE tissue. Glomerular filtration barrier proteins had reduced abundance in the non-clipped kidney of 2K1C hypertensive rats.
“…Desmin is an intermediate filament protein that has also previously been found to be upregulated in podocytes of the non-clipped kidney 2K1C hypertensive rats [50] and is suggested as a marker for glomerular injury in puromycin aminonucleoside nephrosis [51] and diabetic nephropathy [52] in rat models. Transgelin is upregulated in podocytes of several nephropathies [53, 54] and has been reported as markers for repopulating mesangial cells in response to damage [55]. The former was also suggested by our immunohistochemistry findings.…”
BackgroundIt is well known that hypertension may cause glomerular damage, but the molecular mechanisms involved are still incompletely understood.MethodsIn the present study, we used formalin-fixed paraffin-embedded (FFPE) tissue to investigate changes in the glomerular proteome in the non-clipped kidney of two-kidney one-clip (2K1C) hypertensive rats, with special emphasis on the glomerular filtration barrier. 2K1C hypertension was induced in 6-week-old Wistar Hannover rats (n = 6) that were sacrificed 23 weeks later and compared with age-matched sham-operated controls (n = 6). Tissue was stored in FFPE tissue blocks and later prepared on tissue slides for laser microdissection. Glomeruli without severe morphological damage were isolated, and the proteomes were analysed using liquid chromatography–tandem mass spectrometry.Results2K1C glomeruli showed reduced abundance of proteins important for slit diaphragm complex, such as nephrin, podocin and neph1. The podocyte foot process had a pattern of reduced abundance of transmembrane proteins but unchanged abundances of the podocyte cytoskeletal proteins synaptopodin and α-actinin-4. Lower abundance of important glomerular basement membrane proteins was seen. Possible glomerular markers of damage with increased abundance in 2K1C were transgelin, desmin and acyl-coenzyme A thioesterase 1.ConclusionsMicrodissection and tandem mass spectrometry could be used to investigate the proteome of isolated glomeruli from FFPE tissue. Glomerular filtration barrier proteins had reduced abundance in the non-clipped kidney of 2K1C hypertensive rats.
“…Both ACTA2 and ANGPT2 expression is specific for sub-cluster 2, and these genes are markers of the mesangial cells in humans and mice, respectively (Lu et al, 2017b; Scheinman et al, 1976). We also find expression of TAGLN (transgelin), a marker of the migrating mesangial cells that is expressed during glomerular development in the rat embryonic kidney and in human and adult rat kidneys upon injury (Daniel et al, 2012). Fig.…”
The mammalian kidney develops through reciprocal interactions between the ureteric bud and the metanephric mesenchyme to give rise to the entire collecting system and the nephrons. Most of our knowledge of the developmental regulators driving this process arises from the study of gene expression and functional genetics in mice and other animal models. In order to shed light on human kidney development, we have used single-cell transcriptomics to characterize gene expression in different cell populations, and to study individual cell dynamics and lineage trajectories during development. Single-cell transcriptome analyses of 6414 cells from five individual specimens identified 11 initial clusters of specific renal cell types as defined by their gene expression profile. Further subclustering identifies progenitors, and mature and intermediate stages of differentiation for several renal lineages. Other lineages identified include mesangium, stroma, endothelial and immune cells. Novel markers for these cell types were revealed in the analysis, as were components of key signaling pathways driving renal development in animal models. Altogether, we provide a comprehensive and dynamic gene expression profile of the developing human kidney at the single-cell level.
“…Daniel et al [7] reported that Transgelin is upregulated in repopulating mesangial cells and promotes their migratory. However, it was reported that Apigenin induced up-regulation of Transgelin and inhibited invasion and migration in colorectal cell lines [14] .…”
Section: Discussionmentioning
confidence: 99%
“…It is by stabilizing the cytoskeleton through binding to actin that Transgelin plays a role in cell differentiation, cell migration, cell invasion and matrix remodeling [5,6] . Transgelin is upregulated in repopulating mesangial cells, and promotes their migratory and proliferative repair response after injury [7] . The Wuzhishan pig (WZSP) is characterized by its small adult size, and has a mature body weight of only approximately 30 kg with physiological and general biochemical indices very similar to human being.…”
SummaryMesenchymal stem cells (MSCs) are multipotent adult stem cells, can easily be isolated from the bone marrow and subsequently expand in vitro. Bone marrow MSCs (BMMSCs) appear to be poorly immunogenic, and are the most widely used MSCs in tissue regenerative medicine, and the migration capacity of BMMSCs is the key determinant for the efficiency of their regenerative therapy. The Wuzhishan pig (WZSP) is characterized by its physiological and general biochemical indices very similar to humans, and may be potential organ donors for human being owing to its size. In this study, the BMMSCs from WZSP were used to study their migration capacity which regulated by TAGLN in vitro. The specific short hairpin RNA (shRNA) for TAGLN was designed to knock down TAGLN gene, and the scratch assay and transwell migration assay was employed to estimate effect of knockdown TAGLN on the migration capacity of BMMSCs from WZSP. The results showed that the specific shRNA for knocking down TAGLN efficiently was found for the BMMSCs, and there was a significant effect on the migration capacity of the BMMSCs from WZSP with knockdown TAGLN in vitro. In conclusion, TAGLN was an important factor in maintaining the migration capacity of the BMMSCs, which may be benefit for the BMMSCs from WZSP to be used in regenerative therapy for human being.
Keywords: Bone marrow mesenchymal stem cells, Migration capacity, TAGLN, Wuzhishan pig
TAGLN Geninin Bloke Edilmesinin Wuzhishan Domuz Kemik İliği Mezenkimal Kök Hücrelerinde Göç Etme Kapasitesi Üzerine Etkisi
ÖzetMezenkimal kök hücreleri (MSCs) kemik iliğinden kolayca izole edilebilen ve takibinde in vitro olarak çoğalabilen mültipotent olgun kök hücreleridir. Kemik iliği MSC (BMMSC)'lerinin zayıf immunojenik özellikte olduğu görülmekte olup doku yenileme tedavisinde en sıklıkla kullanılan MSC'lerdir ve BMMSC'lerin göç etme kapasiteleri yenileme tedavisindeki başarının anahtarıdır. Wuzhishan domuzu (WZSP) fizyolojik ve genel biyokimyasal belirtileri açısından insana oldukça benzerdir ve boyutu düşünüldüğünde insana organ nakli bakımından oldukça yüksek potansiyele sahiptir. Bu çalışmada WZSP'den elde edilen BMMSC'lerin TAGLN tarafından düzenlenen göç kapasiteleri in vitro olarak çalışıldı. TAGLN için spesifik kısa hairpin RNA (shRNA) TAGLN genini bloke etmek için dizayn edildi. Scratch metodu ve transwell göç metodu bloke TAGLN genin WZSP'den elde edilen BMMSC'lerin göç kapasiteleri üzerine etkisini araştırmak amacıyla uygulandı. Sonuçlar TAGLN genini bloke etmede kullanılan spesifik shRNA'nın BMMSC için etkili olduğunu ve in vitro ortamda TAGLN blokajının WZSP'den elde edilen BMMSC'lerin göç kapasiteleri üzerine anlamlı bir etkisinin var olduğunu gösterdi. Sonuç olarak TAGLN BMMSC'lerde göç kapasitesini sağlamada önemli bir faktördür. Bu durum; WZSP'den elde edilen BMMSC'lerin insanlarda yenileme tedavilerinde kullanılmasına olanak sağlayabilir.
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