BMP-7 enhances SnoN mRNA expression in renal tubular epithelial cells under high-glucose conditions

نویسندگان

  • Yuanyuan Wang
  • Ying Xiao
  • Shuang Li
  • Lei Shi
  • Lirong Liu
  • Yingying Zhang
  • Mingjun Shi
  • Bing Guo
چکیده

The present study aimed to identify any association between bone morphogenetic protein‑7 (BMP‑7) and the expression of the transcriptional co‑repressor Ski‑related novel protein N (SnoN), in addition to alterations in tubulointerstitial fibrosis, during the development and progression of diabetic nephropathy (DN). Streptozotocin was injected into the tail veins of 20 healthy and specific pathogen‑free male Sprague‑Dawley rats. The rats were sacrificed to detect the appropriate biochemical indicators of renal pathological alterations following 24 weeks. Then, various doses of human recombinant BMP‑7 were added to high glucose‑cultured NRK‑52E cells. Immunohistochemistry, immunofluorescence staining and western blotting were used to determine the expression of SnoN, BMP‑7, Smad ubiquitin regulatory factor (Smurf)2, Arkadia, E‑cadherin, α‑smooth muscle actin and Collagen III. Reverse transcription‑quantitative polymerase chain reaction was used to detect SnoN mRNA expression. With the progression of DN, the expression of BMP‑7 in rat renal tissue was downregulated, whereas the expression of Smurf2 and Arkadia increased. Furthermore, the expression of SnoN mRNA increased however the expression of SnoN protein decreased, accompanied by renal tubular epithelial cell mesenchymal transition, extracellular matrix (ECM) deposition and severe renal function disorder. The exogenous recombinant human BMP‑7 alleviated high glucose‑induced phenotypic transformation and ECM synthesis of NRK‑52E in vitro and upregulated SnoN transcription and protein expression, however no effect was observed on the expression of Smurf2 and Arkadia. BMP‑7 may ameliorate DN and renal fibrosis via increasing the expression of SnoN mRNA and protein in renal tubular epithelial cells, rather than directly inhibiting the degradation of SnoN by E3 ubiquitin ligase.

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عنوان ژورنال:

دوره 16  شماره 

صفحات  -

تاریخ انتشار 2017