MAPK/ERK Pathway as a Central Regulator in Vertebrate Organ Regeneration

Abstract

Damage to organs by trauma, infection, diseases, congenital defects, aging, and other injuries causes organ malfunction and is life-threatening under serious conditions. Some of the lower order vertebrates such as zebrafish, salamanders, and chicks possess superior organ regenerative capacity over mammals. The extracellular signal-regulated kinases 1 and 2 (ERK1/2), as key members of the mitogen-activated protein kinase (MAPK) family, are serine/threonine protein kinases that are phylogenetically conserved among vertebrate taxa. MAPK/ERK signaling is an irreplaceable player participating in diverse biological activities through phosphorylating a broad variety of substrates in the cytoplasm as well as inside the nucleus. Current evidence supports a central role of the MAPK/ERK pathway during organ regeneration processes. MAPK/ERK signaling is rapidly excited in response to injury stimuli and coordinates essential pro-regenerative cellular events including cell survival, cell fate turnover, migration, proliferation, growth, and transcriptional and translational activities. In this literature review, we recapitulated the multifaceted MAPK/ERK signaling regulations, its dynamic spatio-temporal activities, and the profound roles during multiple organ regeneration, including appendages, heart, liver, eye, and peripheral/central nervous system, illuminating the possibility of MAPK/ERK signaling as a critical mechanism underlying the vastly differential regenerative capacities among vertebrate species, as well as its potential applications in tissue engineering and regenerative medicine.

TFEB-lysosome pathway activation is associated with different cell death responses to carbon quantum dots in Kupffer cells and hepatocytes

“…This difference may be due to the fundamental difference in the activation pathway induced by CDs between the two hepatocytes. It is known that receptor tyrosine kinases, G-protein-coupled receptors and some cytokine receptors can activate ERK signal transduction pathway [ 65 ]. Different cells can activate different reaction pathways under the stimulation of xenobiotics, which may lead to the differential expression of p-ERK.…”

Characterization of the NGP4A Gene in Regulating Grain Number Per Panicle of Rice (Oryza sativa L.)

“…In the present study, the grain length of ngp4a was significantly affected, which implies that the phenylpropanoid biosynthesis pathway may play multiple roles in the phenotypic mutation of grain number and seed size. MAPK is a serine/threonine protein kinase, whose cascades are highly conserved and is associated with ubiquitous signaling pathways in eukaryotes [40,41]. Plant MAPK signaling modules play fundamental roles in many aspects of biological processes, including immunity, stress responses, and developmental programs [42,43].…”

Molecular mechanisms of exercise contributing to tissue regeneration

“…The extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK), as key members of MAPK family, are also serine/threonine protein kinases that are irreplaceable players participating in diverse biological activities. 310 Similar to PI3K/Akt signaling, MAPK signaling can be activated by a range of growth factors, thus playing an important role in exercise-induced tissue regeneration. More recently, it has been investigated that NRG1/ErbB2 signaling mediates the interaction of YAP with nuclear-envelope and cytoskeletal components for cardiomyocytes regeneration via the activation of ERK.…”