Immunoexpression Pattern of Autophagy-Related Proteins in Human Congenital Anomalies of the Kidney and Urinary Tract

• Published in: International journal of molecular sciences 2024-07, Vol.25 (13), p.6829
• Main Authors: Maglica, Mirko, Kelam, Nela, Perutina, Ilija, Racetin, Anita, Rizikalo, Azer, Filipović, Natalija, Kuzmić Prusac, Ivana, Mišković, Josip, Vukojević, Katarina
• Format: Article
• Language: English
• Subjects: Analysis; Autophagy; Congenital diseases; Endoplasmic Reticulum Chaperone BiP; Genetic disorders; Heat shock proteins; Heat-Shock Proteins - metabolism; HSP70 Heat-Shock Proteins - metabolism; Humans; Kidney - abnormalities; Kidney - metabolism; Kidney - pathology; Kidney diseases; Lysosomal-Associated Membrane Protein 2 - genetics; Lysosomal-Associated Membrane Protein 2 - metabolism; Membranes; Microtubule-Associated Proteins - metabolism; Proteins; Urinary Tract - abnormalities; Urinary Tract - metabolism; Urogenital Abnormalities - metabolism; Urogenital Abnormalities - pathology; Urogenital system; Vesico-Ureteral Reflux - metabolism; Vesico-Ureteral Reflux - pathology
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25136829

The purpose of this study was to evaluate the spatiotemporal immunoexpression pattern of microtubule-associated protein 1 light chain 3 beta (LC3B), glucose-regulated protein 78 (GRP78), heat shock protein 70 (HSP70), and lysosomal-associated membrane protein 2A (LAMP2A) in normal human fetal kidney development (CTRL) and kidneys affected with congenital anomalies of the kidney and urinary tract (CAKUT). Human fetal kidneys (control, horseshoe, dysplastic, duplex, and hypoplastic) from the 18th to the 38th developmental week underwent epifluorescence microscopy analysis after being stained with antibodies. Immunoreactivity was quantified in various kidney structures, and expression dynamics were examined using linear and nonlinear regression modeling. The punctate expression of LC3B was observed mainly in tubules and glomerular cells, with dysplastic kidneys displaying distinct staining patterns. In the control group's glomeruli, LAMP2A showed a sporadic, punctate signal; in contrast to other phenotypes, duplex kidneys showed significantly stronger expression in convoluted tubules. GRP78 had a weaker expression in CAKUT kidneys, especially hypoplastic ones, while normal kidneys exhibited punctate staining of convoluted tubules and glomeruli. HSP70 staining varied among phenotypes, with dysplastic and hypoplastic kidneys exhibiting stronger staining compared to controls. Expression dynamics varied among observed autophagy markers and phenotypes, indicating their potential roles in normal and dysfunctional kidney development.