Pathological insights into activin A: Molecular underpinnings and therapeutic prospects in various diseases.

Autor: Kundra S; Chitkara College of Pharmacy, Chitkara University, Punjab, India., Kaur R; Chitkara College of Pharmacy, Chitkara University, Punjab, India., Pasricha C; Chitkara College of Pharmacy, Chitkara University, Punjab, India., Kumari P; Chitkara College of Pharmacy, Chitkara University, Punjab, India., Gurjeet Singh T; Chitkara College of Pharmacy, Chitkara University, Punjab, India., Singh R; Chitkara College of Pharmacy, Chitkara University, Punjab, India. Electronic address: ravinder.singh@chitkara.edu.in.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Sep 30; Vol. 139, pp. 112709. Date of Electronic Publication: 2024 Jul 19.
DOI: 10.1016/j.intimp.2024.112709
Abstrakt: Activin A (Act A) is a member of the TGFβ (transforming growth factor β) superfamily. It communicates via the Suppressor of Mothers against Decapentaplegic Homolog (SMAD2/3) proteins which govern processes such as cell proliferation, wound healing, apoptosis, and metabolism. Act A produces its action by attaching to activin receptor type IIA (ActRIIA) or activin receptor type IIB (ActRIIB). Increasing circulating Act A increases ActRII signalling, which on phosphorylation initiates the ALK4 (activin receptor-like kinase 4) type 1 receptor which further turns on the SMAD pathway and hinders cell functioning. Once triggered, this route leads to gene transcription, differentiation, apoptosis, and extracellular matrix (ECM) formation. Act A also governs the immunological and inflammatory responses of the body, as well as cell death. Moreover, Act A levels have been observed to elevate in several disorders like renal fibrosis, CKD, asthma, NAFLD, cardiovascular diseases, cancer, inflammatory conditions etc. Here, we provide an update on the recent studies relevant to the role of Act A in the modulation of various pathological disorders, giving an overview of the biology of Act A and its signalling pathways, and discuss the possibility of incorporating activin-A targeting as a novel therapeutic approach for the control of various disorders. Pathways such as SMAD signaling, in which SMAD moves to the nucleus by making a complex and leads to tissue fibrosis in CKD, STAT3, which drives renal fibroblast activity and the production of ECM, Kidney injury molecule (KIM-1) in the synthesis, deposition of ECM proteins, SERCA2a (sarcoplasmic reticulum Ca 2+ ATPase) in cardiac dysfunction, and NF-κB (Nuclear factor kappa-light-chain-enhancer of activated B cells) in inflammation are involved in Act A signaling, have also been discussed.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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