The effect of trehalose on autophagy-related proteins and cyst growth in a hypomorphic Pkd1 mouse model of autosomal dominant polycystic kidney disease

Interdependent Regulation of Polycystin Expression Influences Starvation-Induced Autophagy and Cell Death

“…In one immortalized cystic cell line (OX161) versus one normal renal epithelial cell line (UCL93), autophagy was also reduced [24]. Suppressed autophagic flux was observed in the heart of a hypomorphic Pkd1 mouse model [25] and decreased in the kidney [15]. However, microarray data of ADPKD patient samples did not reveal reduced autophagy, while LC3 was strongly upregulated in cystic tissues of some ADPKD patients [26].…”

“…As such, altered autophagy in late-stage cystic cells could represent a secondary effect rather than a direct effect from polycystin loss (early stage) [12]. In this respect, it is interesting to note that kidney lysates of 70-day-old hypomorphic Pkd1 mice displayed enhanced levels of autophagy markers, while most of these markers were reduced in 120-day-old mice [15]. Here the polycystin-deficient mIMCDs lacked enhanced mTOR activity characteristic of cystic cells, while the PTECs were derived from young early-stage ADPKD patients that carry one mutant PKD1 allele.…”

“…Recently, autophagy has emerged as a possible contributor in ADPKD progression, although the exact nature of its dysregulation in ADPKD remains unresolved [12]. Autophagy was reported to be upregulated, reduced or impaired in various animal models of ADPKD [13][14][15]. PC2 seems to be indispensable for stress-induced autophagy [16][17][18][19], but these studies do not involve renal cells.…”

Improving SIRT1 by trehalose supplementation reduces oxidative stress, inflammation, and histopathological scores in the kidney of aged rats

“…Trehalose is also known to increase autophagy in several models of disorders (Kang et al, 2014;Sarkar et al, 2007). More recently, Atwood et al reported that supplementation with 2% trehalose in water increased markers of autophagy in normal kidneys (Atwood et al, 2020). In addition, trehalose administration was demonstrated to protect against cisplatin-induced acute kidney injury through activation of autophagy (Zhu et al, 2020).…”

“…A fresh solution of 2% trehalose in drinking water was prepared twice a week. We selected this dosage of trehalose according to available data in the literature (Atwood et al, 2020;Berry et al, 2020;Pagliassotti et al, 2017). Young rats received just tap water (n = 7).…”