4 years ago

Quercetin inhibited epithelial mesenchymal transition in diabetic rats, high-glucose-cultured lens, and SRA01/04 cells through transforming growth factor-β2/phosphoinositide 3-kinase/Akt pathway

Diabetic cataract (DC), an identified life-threatening secondary complication of diabetes mellitus, has proven to be a dilemma because of its multifactorial caused and progression. An increasing number of studies have shown that in addition to the maillard reaction, enhanced polyol pathway, and oxidative insults, epithelial mesenchymal transition (EMT) is related to the prevalence of DC. Quercetin, a classic flavonoid with multiple pharmacological effects has been reported to possess therapeutic efficacy in the management and treatment of this disease. However, the mechanism underlying its therapeutic efficacy in EMT of lens epithelial cells (SRA01/04) and contribution to resolving DC remains a mystery. Therefore, in this study, we investigated the effects of quercetin on EMT of SRA01/04 and high-glucose (HG)-induced lens opacity accompanied by lens fibrosis induced by type-1 diabetes. Furthermore, we sought to clarify the specific mechanisms underlying these effects. At week 14 after streptozotocin (STZ) intraperitoneal administration, diabetic rats showed lens opacity accompanied with diminished antioxidant function, enhanced polyol pathway activity, and non-enzymatic glycation. Western blotting confirmed EMT in rat SRA01/04 cells with significantly increased α-smooth muscle actin (α-SMA) and decreased E-cadherin expressions. Treatment of the lens with quercetin ameliorated the oxidative stress, inhibited aldose reductase (AR) activation, reduced advanced glycation end product (AGE) production, and finally suppressed EMT in the early stages. Our in vitro results showed that high-glucose activated the transforming growth factor-β2/phosphoinositide 3-kinase/protein kinase B (TGF-β2/PI3K/Akt) signalling and EMT in SRA01/04 cells. Further, induced oxidative stress, activation of aldose reductase, and accumulation of advanced glycation end products were also involved in this process. Quercetin was potent enough to effectively ameliorate the high glucose (HG)-induced EMT of SRA01/04 cells by inhibiting the activation of TGF-β2/PI3K/Akt, enhancing the antioxidant capacity, inhibiting AR activity, and reducing AGE production. From the whole animal to tissues, and finally the cellular level, our results provide considerable evidence of the therapeutic potential of quercetin for DC. This might be due to its inhibition of EMT mediated through inhibition of the TGF-β/PI3K/Akt pathway.

Publisher URL: www.sciencedirect.com/science

DOI: S0303720717302599

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.