Emergency Department, University Hospital of Split, Spinčićeva 1, 21000 Split, Croatia.
Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Šoltanska 2, 21000 Split, Croatia.
Int J Mol Sci. 2024 Aug 23;25(17):9152. doi: 10.3390/ijms25179152.
Autophagy is the primary intracellular degradation system, and it plays an important role in many biological and pathological processes. Studies of autophagy involvement in developmental processes are important for understanding various processes. Among them are fibrosis, degenerative diseases, cancer development, and metastasis formation. Diabetic kidney disease is one of the main causes of chronic kidney disease and end-stage renal failure. The aim of this study was to investigate the immunohistochemical expression patterns of LC3B, LAMP2A, and GRP78 during different developmental stages of early-developing human kidneys and in samples from patients with type II diabetes mellitus. During the 7/8th DW, moderate expression of LC3B and LAMP2A and strong expression of GRP78 were found in the mesonephric glomeruli and tubules. In the 9/10th DW, the expression of LC3B and LAMP2A was even more pronounced in the mesonephric tubules. LC3B, LAMP2A, and GRP78 immunoreactivity was also found in the paramesonephric and mesonephric ducts and was stronger in the 9/10th DW compared with the 7/8th DW. In addition, the expression of LC3B, LAMP2A, and GRP78 also appeared in the mesenchyme surrounding the paramesonephric duct in the 9/10th DW. In the 15/16th DW, the expression of LC3B in the glomeruli was weak, that of LAMP2A was moderate, and that of GRP78 was strong. In the tubuli, the expression of LC3B was moderate, while the expression of LAMP2A and GRP78 was strong. The strongest expression of LC3B, LAMP2A, and GRP78 was observed in the renal medullary structures, including developing blood vessels. In postnatal human kidneys, the most extensive LC3B, LAMP2A, and GRP78 expression in the cortex was found in the epithelium of the proximal convoluted tubules, with weak to moderate expression in the glomeruli. The medullary expression of LC3B was weak, but the expression of LAMP2A and GRP78 was the strongest in the medullary tubular structures. Significantly lower expression of LC3B was found in the glomeruli of the diabetic patients in comparison with the nondiabetic patients, but there was no difference in the expression of LC3B in the tubule-interstitial compartment. The expression of LAMP2A was significantly higher in the tubule-interstitial compartments of the diabetic patients in comparison with the nondiabetic patients, while its expression did not differ in the glomeruli. Extensive expression of GRP78 was found in the glomeruli and the tubule-interstitial compartments, but there was no difference in the expression between the two groups of patients. These data give us new information about the expression of LC3B, LAMP2A, and GRP78 during embryonic, fetal, and early postnatal development. The spatiotemporal expression of LC3B, LAMP2A, and GRP78 indicates the important role of autophagy during the early stages of renal development. In addition, our data suggest a disturbance in autophagy processes in the glomeruli and tubuli of diabetic kidneys as an important factor in the pathogenesis of diabetic kidney disease.
自噬是主要的细胞内降解系统，在许多生物和病理过程中发挥着重要作用。研究自噬在发育过程中的作用对于理解各种过程非常重要。其中包括纤维化、退行性疾病、癌症发展和转移形成。糖尿病肾病是慢性肾病和终末期肾衰竭的主要原因之一。本研究旨在探讨 LC3B、LAMP2A 和 GRP78 在早期人类肾脏发育的不同阶段以及 2 型糖尿病患者样本中的免疫组织化学表达模式。在 7/8 天 DW 时，中肾肾小球和小管中发现 LC3B 和 LAMP2A 中度表达，GRP78 强表达。在 9/10 天 DW 时，中肾小管中 LC3B 和 LAMP2A 的表达更为明显。在副中肾管和中肾管中也发现了 LC3B、LAMP2A 和 GRP78 免疫反应，与 7/8 天 DW 相比，在 9/10 天 DW 中更强。此外，LC3B、LAMP2A 和 GRP78 的表达也出现在 9/10 天 DW 副中肾管周围的间质中。在 15/16 天 DW 时，肾小球中 LC3B 的表达较弱，LAMP2A 的表达为中等，GRP78 的表达较强。在小管中，LC3B 的表达为中等，而 LAMP2A 和 GRP78 的表达较强。LC3B、LAMP2A 和 GRP78 的最强表达出现在包括发育中的血管在内的肾髓质结构中。在出生后的人类肾脏中，LC3B、LAMP2A 和 GRP78 在皮质中的最广泛表达是在近端曲管的上皮中，肾小球中的表达为弱至中等。LC3B 在髓质中的表达较弱，但在髓质管状结构中 LAMP2A 和 GRP78 的表达最强。与非糖尿病患者相比，糖尿病患者肾小球中 LC3B 的表达明显降低，但在肾小管间质区无差异。与非糖尿病患者相比，糖尿病患者肾小管间质区 LAMP2A 的表达明显升高，而肾小球中无差异。GRP78 在肾小球和肾小管间质区广泛表达，但两组患者之间无差异。这些数据为我们提供了有关 LC3B、LAMP2A 和 GRP78 在胚胎、胎儿和早期新生儿发育过程中的表达的新信息。LC3B、LAMP2A 和 GRP78 的时空表达表明自噬在肾脏早期发育过程中起着重要作用。此外，我们的数据表明，糖尿病肾脏中的自噬过程紊乱是糖尿病肾病发病机制中的一个重要因素。
