Analysis of differential gene expression in stretched podocytes: osteopontin enhances adaptation of podocytes to mechanical stress

Endlich, Nicole; Sunohara, Masataka; Nietfeld, Wilfried; Wolski, Eryk W.; Schiwek, Daniel; Kränzlin, Bettina; Gretz, Norbert; Kriz, Wilhelm; Eickhoff, Holger; Endlich, Karlhans

doi:10.1096/fj.02-0125fje

Cited by 82 publications

(79 citation statements)

References 37 publications

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“…Several investigators have reported that the elevated expression of OPN in vasculature has a crucial role in atherosclerotic calcification [6,8,23,30]; however, the significance of whether the enhancement is inducible or preventive to the vascular calcification has not been fully revealed. In addition, recent studies have shown that, in vascular wall cells, the expression of OPN is accelerated by advanced glycation end-products [31] and mechanical stress [32]. Therefore, it might be considered that these findings can be associated with the mechanism(s) of elevating the plasma OPN level by both aging (Fig.…”

Section: Discussionmentioning

confidence: 97%

Progression of Diabetic Nephropathy Enhances the Plasma Osteopontin Level in Type 2 Diabetic Patients

et al. 2004

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Abstract. Osteopontin (OPN) is thought to play multiple roles in the progression of atherosclerotic plaque including diabetic vascular complications. However, it still remains unclear whether the level of OPN in vivo is indeed clinically associated with the progression of diabetic complications. This study evaluated whether the levels of OPN in plasma and urine are correlated with the progression of diabetic complications, such as retinopathy, neuropathy, and nephropathy in patients with type 2 diabetes. In 229 patients with type 2 diabetes, OPN level in plasma and urine was evaluated by both the severity of diabetic complications, such as retinopathy, neuropathy, and nephropathy, and the clinical characteristics and the substantial laboratory findings. Plasma OPN level increased significantly with aging and the progression of diabetic nephropathy, especially at the stage of renal failure (p<0.05). However, the level was not related to the progression of retinopathy or neuropathy, or to laboratory findings, such as HbA1c or serum lipids. In contrast, urinary OPN level was not associated with diabetic complications in any of the subjects. There was no correlation between the plasma and urinary values of OPN. The results established that the plasma OPN was elevated in proportion to the progression of diabetic nephropathy, indicating that the plasma concentration may be a potential diagnostic predictor of diabetic end-stage renal disease.

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Section: Discussionmentioning

confidence: 97%

Progression of Diabetic Nephropathy Enhances the Plasma Osteopontin Level in Type 2 Diabetic Patients

et al. 2004

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“…Cancer cells produce an FN-rich fibrotic matrix to facilitate metastasis, and both FAK (4, 7) and MYO1E (32) promote carcinogenesis in murine cancer models. In addition, MYO1E protects kidney podocytes from mechanical stressinduced injury, as does SPP1, which may be induced by FAK (33,34). Moreover, keloid formation (i.e., a wound-healing reaction with excessive scar formation) has been associated with MYO1E (35) and FAK function (36).…”

Section: Discussionmentioning

confidence: 99%

Myosin-1E interacts with FAK proline-rich region 1 to induce fibronectin-type matrix

Heim

Squirewell

Neu

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase involved in development and human disease, including cancer. It is currently thought that the four-point one, ezrin, radixin, moesin (FERM)-kinase domain linker, which contains autophosphorylation site tyrosine (Y) 397, is not required for in vivo FAK function until late midgestation. Here, we directly tested this hypothesis by generating mice with FAK Y397-to-phenylalanine (F) mutations in the germline. We found that Y397F embryos exhibited reduced mesodermal fibronectin (FN) and osteopontin expression and died during mesoderm development akin to FAK kinase-dead mice. We identified myosin-1E (MYO1E), an actin-dependent molecular motor, to interact directly with the FAK FERM-kinase linker and induce FAK kinase activity and Y397 phosphorylation. Active FAK in turn accumulated in the nucleus where it led to the expression of osteopontin and other FN-type matrix in both mouse embryonic fibroblasts and human melanoma. Our data support a model in which FAK Y397 autophosphorylation is required for FAK function in vivo and is positively regulated by MYO1E.focal adhesion | myosin | fibronectin | melanoma | cancer F ocal adhesion kinase (FAK) is a nonreceptor tyrosine kinase involved in many biological processes, ranging from mesoderm development to cancer cell metastasis (1). FAK localizes to focal adhesions (2), where it becomes part of a multiprotein complex that links the extracellular matrix (ECM) to the intracellular actin cytoskeleton. FAK is also found in the nucleus, where it is believed to relay information from the cell cortex (3) and induce transcriptional changes (4). The domain architecture of FAK comprises a four-point one, ezrin, radixin, moesin (FERM) domain that is separated from a C-terminal catalytic kinase domain by the FERM-kinase linker. FAK kinase-dead (5) embryos die with mesodermal defects during late gastrulation. In contrast, mice with conditional FAK deletions in the epidermis (6) or breast epithelium (7) show resistance to carcinogenesis.Although FAK has important biological functions, the mechanisms regulating its activity are incompletely understood. For example, it is unclear whether the FERM-kinase linker that contains autophosphorylation site tyrosine (Y) 397 is required for FAK activity in vivo (8). In its closed, inactive conformation, the FAK kinase domain is autoinhibited through interaction with the N-terminal FERM domain. Y397 is nonphosphorylated (9). Upon activation by tethering (10) or other stimuli that induce conformational change (11), the linker region is exposed and Y397 becomes autophosphorylated, leading to the recruitment of the protooncogene SRC. FAK and SRC then form a transient complex, which stabilizes FAK in its active conformation and induces changes in cell shape and focal adhesion turnover in vitro (12). However, mice with a 19-aa deletion in the FAK linker that includes Y397 develop normally until midgestation (8).Here, we have mechanistically discerned the contributions of Y397 to FAK function in viv...

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“…Many factors that facilitate atherosclerosis, such as hypoxia, high plasma glucose, 27 platelet-derived growth factor, 28 AII, 18,29 aldosterone 8 and mechanical stress, 30 also induce OPN expression. OPN has several effects that may facilitate the development and progression of cardiovascular lesions, including cell adhesion, migration, proliferation, angiogenesis and ectopic mineralization.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II receptor blockade with valsartan decreases plasma osteopontin levels in patients with essential hypertension

et al. 2010

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Osteopontin (OPN) has recently emerged as a key factor in both vascular remodelling and development of atherosclerosis. It has been reported that OPN is regulated by the renin-angiotensin-aldosterone system (RAAS). The aim of this study was to clarify the effect of angiotensin II receptor blockade with valsartan on plasma OPN levels in patients with essential hypertension (EHT). Forty-six patients (mean age, 64 ± 11 years) with EHT were randomly assigned to treatment with amlodipine or valsartan. There were no significant differences in baseline clinical characteristics between the two groups. Blood sampling and blood pressure evaluation were performed before and after 24 weeks of treatment. After 24 weeks, both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were decreased significantly and by the same degree in each treatment group. However, valsartan but not amlodipine decreased plasma OPN levels (baseline and 24-week data-valsartan: 614±224 ng ml À1, 472±268 ng ml À1 , P ¼ 0.006; amlodipine: 680 ± 151 ng ml À1 , 687 ± 234 ng ml À1 , P40.999). A positive correlation between the reduction in OPN and the log natural (ln) C-reactive protein (CRP) was seen in the valsartan-treated group. Stepwise regression analysis showed that treatment with valsartan and the reduction of ln CRP were associated with the reduction in OPN levels, and this association was independent of the reduction in SBP or aldosterone levels (valsartan: b ¼ 0.332, P ¼ 0.026; ln CRP reduction: b ¼ 0.366, P ¼ 0.015). These results suggest that suppression of the RAAS and inflammation may decrease plasma OPN levels.

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Analysis of differential gene expression in stretched podocytes: osteopontin enhances adaptation of podocytes to mechanical stress

Cited by 82 publications

References 37 publications

Progression of Diabetic Nephropathy Enhances the Plasma Osteopontin Level in Type 2 Diabetic Patients

Progression of Diabetic Nephropathy Enhances the Plasma Osteopontin Level in Type 2 Diabetic Patients

Myosin-1E interacts with FAK proline-rich region 1 to induce fibronectin-type matrix

Angiotensin II receptor blockade with valsartan decreases plasma osteopontin levels in patients with essential hypertension

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