The Role of Connexin43 in Diabetic Microvascular Complications

Diabetes mellitus is one of the largest global healthcare problems. People with diabetes have high risk of developing any of the microvascularcomplications, including retinopathy, nephropathy, and neuropathy, which can bring much more serious psychological and economic burden for the diabetic patients. As a consequence of its microvascular complications, diabetes has become the leading cause of blindness, end-stage renal disease, and a variety of debilitating neuropathies. Although the mechanisms involved in the development and progression of these three diabetic microvascular complications are different and have not been completely elucidated, some common histopathological features like increased vascular permeability and apoptosis of specific vascular cells are shared in retinopathy and nephropathy. Moreover, epidemiological studies show a significant clinical association between diabetic retinopathy and nephropathy. Connexin43, the most abundant gap junction protein, is ubiquitously expressed in vertebrate tissues and organs including the retina and kidney. Connexin43 has been reported to play a critical role in maintaining vascular homeostasis. In this review, we highlight the role of connexin43 in diabetic microvascular complications, with special focus on diabetic retinopathy and nephropathy.