Abstract

Phosphatase and tensin homolog (PTEN) is a potent tumor suppressor gene that antagonizes the proto-oncogenic phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway and governs basic cellular metabolic processes. Recently, its role in cell growth, metabolism, architecture, and motility as an intramolecular and regulatory mediator has gained widespread research interest as it applies to non-tumorous diseases, such as insulin resistance (IR) and diabetic nephropathy (DN). DN is characterized by renal tubulointerstitial fibrosis (TIF) and epithelial-mesenchymal transition (EMT), and PTEN plays a significant role in the regulation of both. Epigenetics and microRNAs (miRNAs) are novel players in post-transcriptional regulation and research evidence demonstrates that they reduce the expression of PTEN by acting as key regulators of autophagy and TIF through activation of the Akt/mammalian target of rapamycin (mTOR) signaling pathway. These regulatory processes might play an important role in solving the complexities of DN pathogenesis and IR, as well as the therapeutic management of DN with the help of PTEN K27-linked polyubiquitination. Currently, there are no comprehensive reviews citing the role PTEN plays in the development of DN and its regulation via miRNA and epigenetic modifications. The present review explores these facets of PTEN in the pathogenesis of IR and DN.

摘要

磷酸酶和张力蛋白同源物（PTEN）是有效的抑癌基因，可拮抗原癌性磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）信号通路，并控制基本的细胞代谢过程。最近，它在细胞生长，代谢，结构和运动中作为分子内和调节介体的作用已获得广泛的研究兴趣，因为它适用于非肿瘤性疾病，例如胰岛素抵抗（IR）和糖尿病性肾病（DN）。DN的特征是肾小管间质纤维化（TIF）和上皮-间质转化（EMT），PTEN在两者的调节中均起着重要作用。表观遗传学和microRNA（miRNA）是转录后调控中的新角色，研究证据表明，它们通过激活雷帕霉素（mTOR）信号的Akt /哺乳动物靶标充当自噬和TIF的关键调节剂，从而降低了PTEN的表达。这些调节过程可能在解决DN发病机制和IR的复杂性以及借助PTEN K27连接的多泛素化对DN的治疗管理中发挥重要作用。目前，尚无全面的评论指出PTEN在DN的发展及其法规中的作用 以及借助PTEN K27连接的聚泛素化对DN的治疗。目前，尚无全面的评论指出PTEN在DN的发展及其法规中的作用 以及借助PTEN K27连接的聚泛素化对DN的治疗。目前，尚无全面的评论指出PTEN在DN的发展及其法规中的作用通过miRNA和表观遗传修饰。本综述探讨了PTEN在IR和DN发病机理中的这些方面。