Thrombospondin 1 mediates angiotensin II induction of TGF-β activation by cardiac and renal cells under both high and low glucose conditions

Zhou, Yong; Poczatek, Maria H.; Berecek, Kathleen H.; Murphy-Ullrich, Joanne E.

doi:10.1016/j.bbrc.2005.11.060

Cited by 108 publications

(91 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other models of diabetes have also demonstrated increases in TS-1 in cardiac fibroblasts (24), myocytes (25,26), and SMCs (27). TS-1 binding to IAP enhances IGF-I signaling by its ability to modulate the association between IAP and SHPS-1 (13).…”

Section: Discussionmentioning

confidence: 99%

Integrin-Associated Protein Association With Src Homology 2 Domain Containing Tyrosine Phosphatase Substrate 1 Regulates IGF-I Signaling In Vivo

et al. 2008

View full text Add to dashboard Cite

OBJECTIVE-Smooth muscle cell (SMC) maintained in medium containing normal levels of glucose do not proliferate in response to IGF-I, whereas cells maintained in medium containing 25 mmol/l glucose can respond. The aim of this study was to determine whether signaling events that have been shown to be required for stimulation of SMC growth were regulated by glucose concentrations in vivo. RESEARCH DESIGN AND METHODS-We compared IGF-Istimulated signaling events and growth in the aortic smooth muscle cells from normal and hyperglycemic mice.RESULTS-We determined that, in mice, hyperglycemia was associated with an increase in formation of the integrin-associated protein (IAP)/Src homology 2 domaine containing tyrosine phosphatase substrate 1 (SHPS-1) complex. There was a corresponding increase in Shc recruitment to SHPS-1 and Shc phosphorylation in response to IGF-I. There was also an increase in mitogen-activated protein kinase activation and SMC proliferation. The increase in IAP association with SHPS-1 in hyperglycemia appeared to be due to the protection of IAP from cleavage that occurred during exposure to normal glucose. In addition, we demonstrated that the protease responsible for IAP cleavage was matrix metalloprotease-2. An anti-IAP antibody that disrupted the IAP-SHPS-1 association resulted in complete inhibition of IGF-I-stimulated proliferation.CONCLUSIONS-Taken together, our results support a model in which hyperglycemia is associated with a reduction in IAP cleavage, thus allowing the formation of the IAP-SHPS-1 signaling complex that is required for IGF-I-stimulated proliferation of SMC.

show abstract

Section: Discussionmentioning

confidence: 99%

Integrin-Associated Protein Association With Src Homology 2 Domain Containing Tyrosine Phosphatase Substrate 1 Regulates IGF-I Signaling In Vivo

et al. 2008

View full text Add to dashboard Cite

show abstract

“…61 The present findings are unusual in that mesangial sclerosis was not affected by LSKL treatment but albuminuria was reduced. Given the known effects of TSP1 and LSKL peptide on blockade of glucose-stimulated TGF-␤ activity and matrix production by cultured mesangial cells and the reduced mesangial sclerosis in diabetic TSP1 knockout mice, 33,36,64 it is possible that mesangial accessibility of LSKL peptide administered i.p. was insufficient to attenuate glomerulosclerosis, although the effects of LSKL on nephrin expression and glomerular phospho-Smad levels suggest that the peptide is accessible.…”

Section: Discussionmentioning

confidence: 99%

“…30,31 Glucose also increases TSP1 expression by podocytes, 32 and angiotensin II also increases TSP1 expression by renal mesangial cells and cardiac and renal interstitial cells in vitro, which results in increased TGF-␤ activity. 7,31,33 There is also evidence that TSP1-mediated latent TGF-␤ activation is involved in the development of diabetic nephropathy: TSP1 protein is increased in the glomeruli of patients with types 1 and 2 diabetic nephropathy, which correlates with increased TGF-␤ activity. 34,35 Moreover, streptozotocin-treated TSP1 null mice do not develop glomerulosclerosis or podocyte loss, 36 and mice with induced expression of USF2 have increased TSP1 expression, TGF-␤ activity, and renal fibrosis.…”

mentioning

confidence: 99%

Blockade of TSP1-Dependent TGF-β Activity Reduces Renal Injury and Proteinuria in a Murine Model of Diabetic Nephropathy

Miao

Schoeb

et al. 2011

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

Transforming growth factor-␤ (TGF-␤) is key in the pathogenesis of diabetic nephropathy. Thrombospondin 1 (TSP1) expression is increased in diabetes, and TSP1 regulates latent TGF-␤ activation in vitro and in diabetic animal models. Herein, we investigate the effect of blockade of TSP1-dependent TGF-␤ activation on progression of renal disease in a mouse model of type 1 diabetes (C57BL/6J-Ins2 Akita ) as a targeted treatment for diabetic nephropathy. Akita and control C57BL/6 mice who underwent uninephrectomy received 15 weeks of thrice-weekly i.p. treatment with 3 or 30 mg/kg LSKL peptide, control SLLK peptide, or saline. The effects of systemic LSKL peptide on dermal wound healing was assessed in type 2 diabetic mice (db/db). Proteinuria (urinary albumin level and albumin/creatinine ratio) was significantly improved in Akita mice treated with 30 mg/kg LSKL peptide. LSKL treatment reduced urinary TGF-␤ activity and renal phospho-Smad2/3 levels and improved markers of tubulointerstitial injury (fibronectin) and podocytes (nephrin). However, LSKL did not alter glomerulosclerosis or glomerular structure. LSKL did not increase tumor incidence or inflammation or impair diabetic wound healing. These data suggest that selective targeting of excessive TGF-␤ activity through blockade of TSP1-dependent TGF-␤ activation represents a therapeutic strategy for treating diabetic nephropathy that preserves the homeostatic functions of TGF-␤.

show abstract

“…Although several studies have shown that antagonism of angiotensin II signaling results in decreased TGF-b signaling in a variety of tissues, including kidney, lung, skeletal muscle, heart, and aorta (Shihab et al 1997;Sun et al 1998;Lavoie et al 2005;Habashi et al 2006;Yao et al 2006;Cohn et al 2007;Podowski et al 2012), the exact mechanism by which this occurs is not fully understood (Gibbons et al 1992;Stouffer and Owens 1992;Wolf et al 1993Wolf et al , 1999Kagami et al 1994;Lee et al 1995;Campbell and Katwa 1997;Fukuda et al 2000;Boffa et al 2003;Naito et al 2004;RodriguezVita et al 2005;Zhou et al 2006;Chen et al 2013). Suppression of excessive Erk1 and Erk2 MAPK activation with losartan or an inhibitor of MAPK kinase (MAPKK, also known as MEK) has been shown to normalize aortic architecture and aneurysm pathology in MFS mouse models (Habashi et al 2011), indicating that Erk MAPK activation is critical to aneurysm progression.…”

Section: Tgf-b Family Signaling In Connective Tissuesmentioning

confidence: 99%

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

MacFarlane

Haupt

Dietz

et al. 2017

Cold Spring Harb Perspect Biol

View full text Add to dashboard Cite

The transforming growth factor b (TGF-b) family of signaling molecules, which includes TGF-bs, activins, inhibins, and numerous bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs), has important functions in all cells and tissues, including soft connective tissues and the skeleton. Specific TGF-b family members play different roles in these tissues, and their activities are often balanced with those of other TGF-b family members and by interactions with other signaling pathways. Perturbations in TGF-b family pathways are associated with numerous human diseases with prominent involvement of the skeletal and cardiovascular systems. This review focuses on the role of this family of signaling molecules in the pathologies of connective tissues that manifest in rare genetic syndromes (e.g., syndromic presentations of thoracic aortic aneurysm), as well as in more common disorders (e.g., osteoarthritis and osteoporosis). Many of these diseases are caused by or result in pathological alterations of the complex relationship between the TGF-b family of signaling mediators and the extracellular matrix in connective tissues.T he transforming growth factor b (TGF-b) family of cytokines comprises the three TGF-b proteins (TGF-b1, TGF-b2, and TGFb3) and related growth and differentiation factors such as activins, inhibins, bone morphogenic proteins (BMPs), and growth and differentiation factors (GDFs). These molecules play critical roles both in normal development and in several pathological conditions, including inflammation, fibrosis, and cancer (reviewed in Li and Flavell 2006;Gordon and Blobe 2008;Ikushima and Miyazono 2010). This review focuses on the role of these proteins in development and homeostasis of the skeleton and other connective tissues (summarized in Fig. 1) and on the diseases that ensue when these pathways are altered. Aberrant signaling in these pathways has been associated with common connective 6 These authors contributed equally to this work.

show abstract

Thrombospondin 1 mediates angiotensin II induction of TGF-β activation by cardiac and renal cells under both high and low glucose conditions

Cited by 108 publications

References 29 publications

Integrin-Associated Protein Association With Src Homology 2 Domain Containing Tyrosine Phosphatase Substrate 1 Regulates IGF-I Signaling In Vivo

Integrin-Associated Protein Association With Src Homology 2 Domain Containing Tyrosine Phosphatase Substrate 1 Regulates IGF-I Signaling In Vivo

Blockade of TSP1-Dependent TGF-β Activity Reduces Renal Injury and Proteinuria in a Murine Model of Diabetic Nephropathy

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

Contact Info

Product

Resources

About