title: RhoA/mDia-1/profilin-1 signaling targets microvascular endothelial dysfunction in diabetic retinopathy.
abstract: BACKGROUND
  Diabetic retinopathy (DR) is a major cause of blindness in the working-age populations of developed countries, and effective treatments and prevention measures have long been the foci of study. Patients with DR invariably demonstrate impairments of the retinal microvascular endothelium. Many observational and preclinical studies have shown that angiogenesis and apoptosis play crucial roles in the pathogenesis of DR. Increasing evidence suggests that in DR, the small guanosine-5'-triphosphate-binding protein RhoA activates its downstream targets mammalian Diaphanous homolog 1 (mDia-1) and profilin-1, thus affecting important cellular functions, including cell morphology, motility, secretion, proliferation, and gene expression. However, the specific underlying mechanism of disease remains unclear.
  
  
  CONCLUSIONS
  This review focuses on the RhoA/mDia-1/profilin-1 signaling pathway that specifically triggers endothelial dysfunction in diabetic patients. Recently, RhoA and profilin-1 signaling has attracted a great deal of attention in the context of diabetes-related research. However, the precise molecular mechanism by which the RhoA/mDia-1/profilin-1 pathway is involved in progression of microvascular endothelial dysfunction (MVED) during DR has not been determined. This review briefly describes each feature of the cascade before exploring the most recent findings on how the pathway may trigger endothelial dysfunction in DR. When the underlying mechanisms are understood, novel therapies seeking to restore the endothelial homeostasis comprised in DR will become possible.
authors: Department of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, No.100 Haining Road, Shanghai, 200080, China.
authors: Qianyi
authors: Q
authors: Lu
authors: Li
authors: L
authors: Lu
authors: Wei
authors: W
authors: Chen
authors: Haibing
authors: H
authors: Chen
authors: Xun
authors: X
authors: Xu
authors: Zhi
authors: Z
authors: Zheng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000503:physiopathology*; D042783:Endothelial Cells / Q000378:metabolism*; D000080865:Formins; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D055806:Microvessels; D051304:Profilins / Q000502:physiology*; D015861:Retinal Neovascularization / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C108962:DIAPH1 protein, human; D000080865:Formins; D051304:Profilins; D020742:rhoA GTP-Binding Protein