Metabolic reprogramming in keloid fibroblasts: Aerobic glycolysis and a novel therapeutic strategy

Qi Li1, Zelian Qin1, Fangfei Nie1

  • 1Department of Plastic and Reconstructive Surgery, Peking University Third Hospital, Beijing, 100191, China.

Insights

Keloid fibroblasts exhibit aerobic glycolysis, a metabolic shift crucial for their growth. Inhibiting this process, known as the Warburg effect, shows potential for keloid treatment.

Area of Science:

  • Dermatology
  • Metabolic research
  • Cancer biology (Warburg effect)

Background:

  • Keloids are fibroproliferative skin lesions linked to metabolic disturbances.
  • The specific metabolic pathways driving keloid pathogenesis are not well understood.

Purpose of the Study:

  • To investigate the role of glycolytic reprogramming in keloid development.
  • To evaluate glycolysis inhibition as a potential therapeutic strategy for keloids.

Main Methods:

  • Compared metabolic profiles of normal skin fibroblasts (NFs) and keloid fibroblasts (KFs) using intracellular metabolic assays.
  • Analyzed gene and protein expression of glycolytic enzymes.
  • Assessed the impact of 2-deoxy-glucose (2-DG) on KF proliferation.

Main Results:

  • Keloid fibroblasts (KFs) display a metabolic shift towards aerobic glycolysis (Warburg effect) compared to NFs.
  • KFs show increased glycolysis, glycolytic capacity, glucose uptake, and lactate production.
  • Upregulated expression of glycolytic enzymes was observed in KFs.
  • Glycolysis inhibition with 2-DG significantly suppressed KF proliferation.

Conclusions:

  • Keloids exhibit a reprogrammed metabolic phenotype characterized by aerobic glycolysis.
  • This metabolic reprogramming is essential for keloid hyperplasia.
  • Targeting glycolysis with inhibitors presents a promising therapeutic avenue for keloid treatment.

Related Concept Videos

What is Glycolysis?00:56

What is Glycolysis?

Overview
Cells make energy by breaking down macromolecules. Cellular respiration is the biochemical process that converts "food energy" (from the chemical bonds of macromolecules) into chemical energy in the form of adenosine triphosphate (ATP). The first step of this tightly regulated and intricate process is glycolysis. The word glycolysis originates from the Latin glyco (sugar) and lysis (breakdown). Glycolysis serves two main intracellular functions: generating ATP and generating...
178.4K
Outcomes of Glycolysis01:13

Outcomes of Glycolysis

Nearly all the energy used by cells comes from the bonds that make up complex organic compounds. These organic compounds are broken down into simpler molecules, such as glucose. As a result, cells extract energy from glucose over many chemical reactions—a process called cellular respiration.
Cellular respiration can occur aerobically (with oxygen) or anaerobically (without oxygen). In the presence of oxygen, cellular respiration starts with glycolysis and continues with pyruvate...
107.8K
Energy-releasing Steps of Glycolysis01:28

Energy-releasing Steps of Glycolysis

Glycolysis is divided into two phases based on whether energy is utilized or released. While the first phase consumes ATP, the second phase produces energy in the form of ATP and NADH. The energy is released over a sequence of reactions that turns G3P into pyruvate. The energy-releasing phase—steps 6-10 of glycolysis—occurs twice, once for each of the two 3-carbon sugars produced during steps 1-5 of the first phase.
The first energy-releasing step—the 6th step of glycolysis...
147.3K
Energy-requiring Steps of Glycolysis01:20

Energy-requiring Steps of Glycolysis

Glucose is the source of nearly all energy used by organisms. The first step of converting glucose into usable energy is called glycolysis. Glycolysis occurs in the cytosol of the cell over two phases: an energy-requiring phase and an energy-releasing phase. Over the first three steps, glucose is converted into different forms and attached to two phosphate groups donated by two ATP molecules, resulting in an unstable sugar. In the next two stages, the unstable sugar splits into two sugar...
172.2K
Glycolysis01:23

Glycolysis

Glycolysis, the Embden-Meyerhof pathway, is a central metabolic pathway involved in glucose catabolism. It is highly conserved across most organisms, reflecting its fundamental role in cellular energy production. This process occurs in the cytoplasm and can function both in the presence and absence of oxygen, making it versatile for various organisms and environmental conditions.Stages of GlycolysisGlycolysis is a ten-step pathway that converts glucose into pyruvate, generating a net gain of...
1.8K
What is Metabolism?00:52

What is Metabolism?

Overview
132.7K