Introduction
The basic cellular process of degradation and recycling of damaged cellular components is autophagy. The process does play an important role in the maintenance of cellular homeostasis. In recent years, it has come under more attention regarding its significance in kidney diseases, especially on its impact on renal fibrosis and tissue repair. Kidney fibrosis is a hallmark of chronic kidney disease and is characterized by excess deposition of extracellular matrix proteins leading to progressive renal failure. Given its role in modulating cellular stress responses and inflammation, autophagy has emerged as one of the promising therapeutic targets for managing renal fibrosis. These findings elucidate further into the role of autophagy in fibrosis of the kidney and its role in relating to tissue repair mechanisms, potentially providing new therapeutic avenues that can inhibit the progression of CKD.
Understanding Autophagy and its Cellular Functions
A lysosomal pathway is the mechanism in the cells through which damaged proteins, organelles, and other cellular components are degraded. Sequestration of targeted materials into autophagosomes leads to fusion with lysosomes for degradation. The general effect of autophagy is usually activated in response to cellular stressors such as nutrient deprivation, oxidative stress, and hypoxia in the injured kidney.
The function of autophagy in kidney cells, especially renal tubular epithelial cells, has been proven to modulate several key functions, namely maintaining cellular energy balance, protection against oxidative stress, and modulation of inflammatory responses. The role becomes even more prominent during episodes of AKI, where it promotes cellular recovery and adaptation to stress.
Dual Role of Autophagy in Kidney Fibrosis
For the majority of chronic kidney diseases, the final common pathway is kidney fibrosis, which results from persistent inflammation and activation of the fibrogenic pathways. Tissue myofibroblast activation produces large amounts of the ECM components, such as collagen, which cause tissue scarring. Thus, a role of autophagy in the development of fibrosis, although generally considered protective through an enhancement of cell survival, is more complex.
In certain conditions, autophagy has been demonstrated to be antifibrotic as it breaks down pro-fibrotic proteins and inhibits the activation of myofibroblasts. For example, enhanced UUO-induced renal fibrosis in models of autophagy in renal tubular epithelial cells was associated with decreased levels of collagen deposition and accumulation of ECM. The ability of autophagy to break down mature TGF-β—the central activator of fibrosis—also suggests its antifibrotic role. The impairment of autophagy results in overactivation of fibrogenic signaling pathways, with the effect exerted through excessive matrix deposition and fibrosis.
Although it may have sometimes pro-fibrotic effects in a certain cell context and at a specific stage of a disease, autophagy can be implicated in the regulation of fibrosis. Indeed, it was reported to support the survival of myofibroblasts and, accordingly, enhance the development of fibrosis. The dual role of autophagy as protective and deleterious implies that its timing and regulation are relevant to determining its impact on fibrosis in the kidney.