Transforming growth factor-β1 and diabetic nephropathy

Chang, Albert S.; Hathaway, Catherine K.; Smithies, Oliver; Kakoki, Masao

doi:10.1152/ajprenal.00502.2015

Cited by 164 publications

(134 citation statements)

References 121 publications

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“…26 Among such cytokines, the transforming growth factor-β1 (TGF-β1) is believed to have a central role as a mediator in the fibrogenic process of diabetic nephropathy. 27 In the current study, TGF-β1 was not detected in the renal cortex of control group I. On the other hand, diabetic rats in group III showed a positive TGF-β1immune-reaction in affected renal corpuscles and tubules.…”

Section: Discussioncontrasting

confidence: 53%

Impact of nanoparticle albumin-bound paclitaxel on microscopic structure and immunohistochemical expression of transforming growth factor-β1 in the renal cortex of rat diabetic nephropathy

Mazroa

Asker

2016

Int J Sci Rep

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Background: Diabetic nephropathy is a serious complication of diabetes. A low dose of paclitaxel drug ameliorates fibrosis in different diseases. Nano-particle albumin–bound paclitaxel (nab-paclitaxel) is a novel formula of paclitaxel approved in many countries.Methods:This study aimed to investigate the effect of nab-paclitaxel on microscopic structure and immunohistochemical expression of transforming growth factor-β1 (as a fibrogenic mediator) in the renal cortex of rat diabetic nephropathy. Forty five adult rats were divided into; group I (control), group II (receiving nab-paclitaxel), group III (diabetic) and group IV (diabetic rats receiving nab-paclitaxel). After 4 weeks, kidneys were prepared for light microscopy and TGF- β1 immunohistochemical study.Results: Renal cortex in group II had a microscopic structure similar to group I. TGF- β1 immune-reaction was negative in group I and II. Group III showed microscopic diabetic changes as hypertrophied renal corpuscles, expanded mesangial matrix, degenerated tubules, interstitial inflammatory cells infiltration, and glomerular and tubulo-interstitial fibrosis. A positive TGF- β1 immune-reaction was detected in renal corpuscles and tubules. In group IV, diabetic changes were relatively ameliorated with decreased TGF-β1immune-expression.Conclusions:Nab-paclitaxel partially ameliorated microscopic structural changes in renal cortex of rats with diabetic nephropathy and decreased TGF-β1 immune-expression, suggesting a partial reno-protective effect of nab-paclitaxel in diabetic nephropathy.

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Section: Discussioncontrasting

confidence: 53%

Impact of nanoparticle albumin-bound paclitaxel on microscopic structure and immunohistochemical expression of transforming growth factor-β1 in the renal cortex of rat diabetic nephropathy

Mazroa

Asker

2016

Int J Sci Rep

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“…It is considered to be the strongest cytokine involved in glomerulosclerosis in diabetic nephropathy [19]. We found that the TGF-β1 level in diabetic rats was significantly higher than in the controls.…”

Section: Changes In Icam-1 Mcp-1 Tgf-β1 In Rat Renal Tissuementioning

confidence: 60%

High Mobility Group Box1 Inhibitor Glycyrrhizic Acid Attenuates Kidney Injury in Streptozotocin-Induced Diabetic Rats

Zhang

Chen

et al. 2017

Kidney Blood Press Res

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Background/Aims: High mobility group box 1 (HMGB1) is an important mediator of the inflammatory response. It has been implicated in the pathogenesis of autoimmune diseases, atherosclerosis, and obesity. However, the effects of HMGB1 on diabetic nephropathy remain unclear. Here, we investigated the potential roles and mechanisms of an HMGB1 inhibitor, glycyrrhizic acid (GA), in renal injury with the streptozotocin (STZ)-induced rat model. Methods: The diabetic rat was generated by intraperitoneal injection of STZ and then treated with the HMGB1 inhibitor GA or saline for 8 weeks. Rats were randomly divided into three groups: the normal control and saline group (Control), the diabetic rats with saline group (Diabetic) and the diabetic rats plus GA group (Diabetic+GA). Peripheral blood was obtained for measurements of blood glucose, TNF-a, IL-6 and IL-1β. The mRNA levels of proinflammatory cytokines (TNF-a, IL-6 and IL-1β), chemokines (MCP-1), intercellular adhesion molecules (ICAM-1) and TGF-β1 in the kidneys were evaluated by quantitative real-time PCR. The protein levels of phosphorylated(p) and total(t) p38 MAPK, JNK, ERK, and NF-κB were measured by western blot. Results: We found that diabetic rats showed obvious renal lesions, an elevated urinary albumin/creatinine ratio (UACR) and increased expression levels of TGF-β1 and Col-IV in the kidneys, accompanied by significantly enhanced expression levels of HMGB1, receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR-4) in the kidney tissue. Furthermore, the GA treatment significantly reduced the UAC levels, ameliorated renal injury, and decreased the TNF-α, 1L-6, IL-1β, MCP-1, ICAM-1, TGF-β1 and Col-IV levels. Importantly, the expression levels of HMGBI, RAGE and TLR4 in the kidney tissues of the diabetic rats were also inhibited by the GA treatment. Furthermore, the GA treatment significantly reduced the phosphorylation levels of ERK and p38 MAPK and suppressed NF-κB translocation from the cytoplasm to the nucleus. Conclusion: Our findings indicate that the HMGB1 inhibitor GA may improve renal injury and inflammatory responses in diabetic rats by regulating RAGE/TLR4-related ERK and p38 MAPK/NF-κB activation.

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“…4 F‐H ). We found that TGF‐β, a key mediator of extracellular matrix overproduction and glomerulosclerosis (25), was dramatically increased in diabetic mice but was significantly lower in Nlrc5 ‐/‐ ‐STZ compared with WT‐STZ mice (Fig. 4 I, J ).…”

Section: Resultsmentioning

confidence: 95%

NLRC5 deficiency ameliorates diabetic nephropathy through alleviating inflammation

et al. 2018

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NOD-like receptor family caspase recruitment domain family domain containing 5 (NLRC5) has important roles in inflammation and innate immunity. NLRC5 was highly expressed in kidney from streptozotocin-induced diabetic mice, db/ db mice and patients with diabetes. Based on that evidence, the present study was designed to explore the roles of NLRC5 in the progression of diabetic nephropathy (DN). We examined kidney injury, including inflammation and fibrosis in Nlrc5 gene knockout ( Nlrc5) and wild-type (WT) diabetic mice. We found that Nlrc5 mice developed less-severe diabetic kidney injury compared with WT mice, exhibiting lower albuminuria, less fibronectin and collagen IV expression, and reduced macrophage infiltration but greater levels of podocin and nephrin in the diabetic kidney. The underlying mechanisms were further investigated in vitro with peritoneal macrophages and mesangial cells treated with high glucose. Reduced proinflammatory effect was observed in peritoneal macrophages from Nlrc5 mice, associated with NF-κB pathway suppression. Knocking down of NLRC5 in mesangial cells in high-glucose conditions was also associated with reduced NF-κB and TGF-β/Smad signaling. Taken together, NLRC5 promotes inflammation and fibrosis during DN progression partly through the effects on NF-κB and TGF-β/Smad pathways. NLRC5 may, therefore, be a promising therapeutic target for DN treatment.-Luan, P., Zhuang, J., Zou, J., Li, H., Shuai, P., Xu, X., Zhao, Y., Kou, W., Ji, S., Peng, A., Xu, Y., Su, Q., Jian, W., Peng, W. NLRC5 deficiency ameliorates diabetic nephropathy through alleviating inflammation.

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Transforming growth factor-β1 and diabetic nephropathy

Cited by 164 publications

References 121 publications

Impact of nanoparticle albumin-bound paclitaxel on microscopic structure and immunohistochemical expression of transforming growth factor-β1 in the renal cortex of rat diabetic nephropathy

Impact of nanoparticle albumin-bound paclitaxel on microscopic structure and immunohistochemical expression of transforming growth factor-β1 in the renal cortex of rat diabetic nephropathy

High Mobility Group Box1 Inhibitor Glycyrrhizic Acid Attenuates Kidney Injury in Streptozotocin-Induced Diabetic Rats

NLRC5 deficiency ameliorates diabetic nephropathy through alleviating inflammation

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