A matter of regeneration and repair: caspases as the key molecules

Abstract

Researchers have been focused on understanding the pathogenesis of human diseases. They have been working to find the roles of caspases in the balance between apoptosis, autophagy, pyroptosis, and necroptosis, and also in the regeneration of damaged tissue. At this point, besides their death-inducing roles, new findings indicate the role of caspases in proliferation for maintaining the viability of cells in response to signals from apoptotic cells. Recently, determining cell fate has also been identified among other functions of caspases. Findings indicate that caspases direct cellular pathways to cell differentiation by suppressing stem cell self-renewal. The common opinion about the related mechanism is that low and transient caspase activation leads to terminal differentiation by affecting the expression of key genes related to differentiation. Moreover, caspases are essential proteases in the regulation and modulation of the repair process. In repair, they have roles in apoptosis, release of inflammatory cytokines and chemokines, promotion of cell migration, and immune cell infiltration. However, paracrine signaling through caspase activation leads to cell proliferation after cancer therapy and causes tumor relapse, which complicates the current therapy. In this scope, we have reviewed the main mechanisms of pathological, regenerative, and restorative effects of caspases.

Effect of leucine on NF-κB pathway in liver regeneration after partial hepatectomy in rats, as determined by miniarray analysis

“…It is an interesting fi nding that the Group III showed both an increased expression of genes activating NF-κB signal pathway and Casp8 gene. Nevertheless, one study revealed that Casp8 might also have proliferative effect apart from its apoptotic effect (30).…”

Characterization of the Apoptotic and Antimicrobial Activities of Two Initiator Caspases of Sea Cucumber Apostichopus japonicus

“…To date, at least 18 CASPs have been reported in mammals [9]. Among them, CASP2 and CASP9, which share similar structures, function mainly as apoptosis cascade mediators [10,11].…”

Genome‐wide characterization of caspase genes in Japanese pufferfish, Takifugu rubripes, and expression profiles in response to Vibrio harveyi infection

“…Because of the discrepancies in the caspases, 18 caspase genes have been confirmed in mammals (Eckhart et al, 2008). However, three caspases (casp15, casp17, and casp18) cannot be found in placental mammals (Shalini et al, 2015), and 14 caspases have been reported in fish thus far (Bolkent et al, 2016;Takle & Andersen, 2007). In Takifugu genus, only five caspase genes have been identified and characterized (Casp2, Casp3, Casp6, Casp7, and Casp8 of Takifugu obscurus) (Fu et al, 2018(Fu et al, , 2019(Fu et al, , 2020; however, no study has been conducted to characterize caspases in Japanese pufferfish.…”