Functional Characterization of the Lin28/let-7 Circuit During Forelimb Regeneration in Ambystoma mexicanum and Its Influence on Metabolic Reprogramming

Abstract

The axolotl (Ambystoma mexicanum) is a caudate amphibian, which has an extraordinary ability to restore a wide variety of damaged structures by a process denominated epimorphosis. While the origin and potentiality of progenitor cells that take part during epimorphic regeneration are known to some extent, the metabolic changes experienced and their associated implications, remain unexplored. However, a circuit with a potential role as a modulator of cellular metabolism along regeneration is that formed by Lin28/let-7. In this study, we report two Lin28 paralogs and eight mature let-7 microRNAs encoded in the axolotl genome. Particularly, in the proliferative blastema stage amxLin28B is more abundant in the nuclei of blastemal cells, while the microRNAs amx-let-7c and amx-let-7a are most downregulated. Functional inhibition of Lin28 factors increase the levels of most mature let-7 microRNAs, consistent with an increment of intermediary metabolites of the Krebs cycle, and phenotypic alterations in the outgrowth of the blastema. In summary, we describe the primary components of the Lin28/let-7 circuit and their function during axolotl regeneration, acting upstream of metabolic reprogramming events.

Lin28 Enhances Glucose Metabolism in Human Placental Mesenchymal Stem Cells during Hypoxia via the PI3K-Akt Pathway

“…Next, we studied the effects of Lin28 on LDHA. Lin28 can downregulate members of the microRNA Let-7 family by binding to the microRNA Let-7 precursor [42,43]. Our experiment also veri ed these reports.…”

Lin28 promoting the protective effect of PMSCs on hepatic ischaemia–reperfusion injury by regulating glucose metabolism

“…Next, we studied the effects of Lin28 on LDHA. Lin28 can downregulate members of the microRNA Let‐7 family by binding to the microRNA Let‐7 precursor 46,47 . Our experiments also verified these findings.…”

“…Lin28 can downregulate members of the microRNA Let-7 family by binding to the microRNA Let-7 precursor. 46,47 Our experiments also verified these findings. Further, the increased expression of LDHA under hypoxia allows cells to switch from oxidative phosphorylation to anaerobic glycolysis.…”

Antineoplastic Activity of Rhus trilobata Nutt. (Anacardiaceae) against Ovarian Cancer and Identification of Active Metabolites in This Pathology

“…or Vectashield ® /DAPI mounting medium (Vector Laboratories ® ), depending on each assay. Finally, observations were conducted using light microscopy (BX41, Olympus ® , Miami, FL, USA) or confocal microscopy (LSM 700, Zeiss ® , Pleasanton, CA, USA) [30].…”