Mukhi Dhanunjay, Nishad Rajkishor, Menon Ram K, Pasupulati Anil Kumar
Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, India.
Department of Pediatric Endocrinology and Physiology, University of Michigan, Ann Arbor, MI, United States.
Front Med (Lausanne). 2017 Jul 12;4:102. doi: 10.3389/fmed.2017.00102. eCollection 2017.
The kidney regulates water, electrolyte, and acid-base balance and thus maintains body homeostasis. The kidney's potential to ensure ultrafiltered and almost protein-free urine is compromised in various metabolic and hormonal disorders such as diabetes mellitus (DM). Diabetic nephropathy (DN) accounts for ~20-40% of mortality in DM. Proteinuria, a hallmark of renal glomerular diseases, indicates injury to the glomerular filtration barrier (GFB). The GFB is composed of glomerular endothelium, basement membrane, and podocytes. Podocytes are terminally differentiated epithelial cells with limited ability to replicate. Podocyte shape and number are both critical for the integrity and function of the GFB. Podocytes are vulnerable to various noxious stimuli prevalent in a diabetic milieu that could provoke podocytes to undergo changes to their unique architecture and function. Effacement of podocyte foot process is a typical morphological alteration associated with proteinuria. The dedifferentiation of podocytes from epithelial-to-mesenchymal phenotype and consequential loss results in proteinuria. Poorly controlled type 1 DM is associated with elevated levels of circulating growth hormone (GH), which is implicated in the pathophysiology of various diabetic complications including DN. Recent studies demonstrate that functional GH receptors are expressed in podocytes and that GH may exert detrimental effects on the podocyte. In this review, we summarize recent advances that shed light on actions of GH on the podocyte that could play a role in the pathogenesis of DN.
肾脏调节水、电解质和酸碱平衡，从而维持机体的内环境稳定。在各种代谢和激素紊乱疾病（如糖尿病）中，肾脏确保产生超滤过且几乎无蛋白尿液的能力会受到损害。糖尿病肾病（DN）约占糖尿病患者死亡率的20 - 40%。蛋白尿是肾小球疾病的一个标志，表明肾小球滤过屏障（GFB）受损。GFB由肾小球内皮、基底膜和足细胞组成。足细胞是终末分化的上皮细胞，复制能力有限。足细胞的形状和数量对于GFB的完整性和功能都至关重要。足细胞易受糖尿病环境中各种有害刺激的影响，这些刺激可能促使足细胞的独特结构和功能发生改变。足细胞足突消失是与蛋白尿相关的典型形态学改变。足细胞从上皮表型向间充质表型的去分化及随之而来的丢失会导致蛋白尿。1型糖尿病控制不佳与循环生长激素（GH）水平升高有关，GH与包括DN在内的各种糖尿病并发症的病理生理学有关。最近的研究表明，功能性GH受体在足细胞中表达，并且GH可能对足细胞产生有害影响。在本综述中，我们总结了近期的进展，这些进展揭示了GH对足细胞的作用，而这可能在DN的发病机制中起作用。
