Postn, also known as periostin, is an extracellular matrix protein. It is involved in multiple biological processes, such as extracellular matrix remodeling, and is associated with pathways like Wnt/β -catenin, NF -κB, and IL -6/STAT3. It plays a significant role in various biological contexts, including tissue fibrosis, tumor development, and immune regulation [3,6-9]. Genetic models, especially KO/CKO mouse models, can be valuable in further understanding its functions.

In cancer, POSTN + cancer-associated fibroblasts (CAFs) act as immune response barriers. In hepatocellular carcinoma, they hinder T-cell infiltration and reduce immunotherapy efficacy, and interact with SPP1 + macrophages via the IL -6/STAT3 signaling pathway [1]. In non-small cell lung cancer, POSTN + CAFs are enriched in advanced tumors, associate with SPP1 + macrophages, and are related to immune suppression and poor prognosis [2]. In gastric cancer, POSTN secreted by CAFs enhances macrophage chemotaxis through the Akt signaling pathway, leading to immune checkpoint blockade resistance [8]. In acne keloidalis, communication between POSTN + fibroblasts and SPP1 + myeloid cells via the SPP1 axis may contribute to pathogenesis [3].

In idiopathic pulmonary fibrosis, POSTN is up-regulated and may contribute to fibrosis, as knockdown of POSTN attenuates fibrotic marker expression in response to TGF -β1 stimulation [4]. In neuroblastoma, ALK drives tumorigenesis in part through a feedforward loop between POSTN and WNT signaling, and knockdown of POSTN delays adhesion and suppresses proliferation of ALK/MYCN tumors [5]. In intervertebral disc degeneration, POSTN promotes nucleus pulposus cell senescence and extracellular matrix metabolism via activating the Wnt/β -catenin and NF -κB signal pathway, and its inhibition can ameliorate the disease progression [6]. In heart failure, interactions between C-C chemokine receptor type 2 (CCR2) macrophages and fibroblasts mediated by interleukin-1β (IL-1β) signalling drive the emergence of FAP/POSTN fibroblasts, and targeting this signaling reduces myocardial fibrosis and improves cardiac function [7].

In conclusion, Postn is crucial in processes like extracellular matrix remodeling, immune regulation, and tissue fibrosis. Model-based research, especially KO/CKO mouse models, has revealed its role in various diseases, including cancer, fibrosis-related diseases, and heart failure. Understanding Postn provides insights into disease mechanisms and potential therapeutic targets.