Autophagy in renal fibrosis: Protection or promotion?

Abstract

Autophagy is a process that degrades endogenous cellular protein aggregates and damaged organelles via the lysosomal pathway to maintain cellular homeostasis and energy production. Baseline autophagy in the kidney, which serves as a quality control system, is essential for cellular metabolism and organelle homeostasis. Renal fibrosis is the ultimate pathological manifestation of progressive chronic kidney disease. In several experimental models of renal fibrosis, different time points, stimulus intensities, factors, and molecular mechanisms mediating the upregulation or downregulation of autophagy may have different effects on renal fibrosis. Autophagy occurring in a single lesion may also exert several distinct biological effects on renal fibrosis. Thus, whether autophagy prevents or facilitates renal fibrosis remains a complex and challenging question. This review explores the different effects of the dual regulatory function of autophagy on renal fibrosis in different renal fibrosis models, providing ideas for future work in related basic and clinical research.

Autophagy in intestinal fibrosis: relevance in inflammatory bowel disease

“…Li et al, 2020). In addition, the protective role of autophagy at the renal level has been demonstrated in other models, such as rapamycin, Beclin1 +/− , LC3 −/− (Ding et al, 2014) , ATG5-KO (Kimura et al, 2011) or ATG7-KO (Kawakami et al, 2015), where autophagy helps to control the accumulation of collagen and cytokines, cell infiltration, inhibition of EMT processes and reactive oxygen species clearance (Dai et al, 2022).…”

“…Chen et al, 2013)]. Signalling pathways capable of altering autophagic markers (WNT/WISP1, Myc or CHOP) or autophagosome-lysosome fusion controllers (LAMP2) have been related to fibrotic processes in the kidney (Dai et al, 2022).…”

Cordyceps cicadae ameliorates inflammatory responses, oxidative stress, and fibrosis by targeting the PI3K/mTOR‐mediated autophagy pathway in the renal of MRL/lpr mice

“…Autophagy, which is an important stress‐responsive system, has been implicated in the pathophysiology of several renal disorders, including renal fibrosis 8,9 . Although autophagy is not required for renal formation, it is important in adult renal resident cells and is closely linked to the progression of renal fibrosis 10 .…”

“…Autophagy, which is an important stress‐responsive system, has been implicated in the pathophysiology of several renal disorders, including renal fibrosis. 8 , 9 Although autophagy is not required for renal formation, it is important in adult renal resident cells and is closely linked to the progression of renal fibrosis. 10 Cellular stressors, including hypoxia, reactive oxygen species, stress on the endoplasmic reticulum (ER), damage to DNA, invasive infections, and immunological signals, can trigger autophagy.…”

Autophagy in peritoneal fibrosis

“…In multiple experimental models, pharmacological and genetic interventions that impair autophagy were found to promote or exacerbate diseases ( Klionsky et al, 2021 ). Autophagy plays a critical role in the progression of fibrosis in various organs, such as the kidneys ( Dai et al, 2022 ), liver ( Sun et al, 2021 ), and lungs ( Araya et al, 2013 ). However, the causal connection between autophagy and PF and the pathophysiological mechanisms remains unclear.…”