Crebl2, also known as cAMP response element-binding protein-like 2, is a bZIP_1 protein involved in multiple biological processes. It participates in regulating cellular metabolism, with its functions related to the mTORC1 pathway, and also plays a role in adipogenesis and lipogenesis through interaction with CREB [1,3].

In functional studies, Crebl2 knockdown in C2C12 myoblasts led to elevated glucose uptake, glycolysis, and triglyceride biosynthesis, while in Hepa1-6 hepatoma cells, it caused increased triglyceride levels, indicating its role as a regulator of cellular metabolism [1]. In liver fibrosis research, HSCs-specific Crebl2 deletion ameliorated PTH-induced liver fibrosis in CCl4-treated mice, showing that PTH1R signaling regulates collagen production in HSCs through the Crebl2/SMAD3/TGFβ regulatory circuits [2]. In 3T3-L1 adipocytes, CREBL2 knockdown restrained adipogenic conversion and lipogenesis, and depletion of CREB could block the adipogenic effects of overexpressed CREBL2 [3]. In Schwann cells, miR-195-5p downregulated Crebl2, modulating Schwann cell functions and contributing to peripheral nerve regeneration [4].

In conclusion, Crebl2 is a crucial regulator in cellular metabolism, adipogenesis, liver fibrosis, and peripheral nerve repair. Gene knockout or knockdown models, like those in muscle, liver, HSCs, adipocytes, and Schwann cells, have revealed its functions in these biological processes, providing insights into related disease mechanisms such as liver fibrosis and potentially guiding future therapeutic strategies in these disease areas.

References:

1. Tiebe, Marcel, Lutz, Marilena, Senyilmaz Tiebe, Deniz, Teleman, Aurelio A. 2019. Crebl2 regulates cell metabolism in muscle and liver cells. In Scientific reports, 9, 19869. doi:10.1038/s41598-019-56407-w. https://pubmed.ncbi.nlm.nih.gov/31882710/

2. Hong, Ting, Xiong, Xuelian, Chen, Yaqiong, Lu, Yan, Li, Xiaoying. 2023. Parathyroid hormone receptor-1 signaling aggravates hepatic fibrosis through upregulating cAMP response element-binding protein-like 2. In Hepatology (Baltimore, Md.), 78, 1763-1776. doi:10.1097/HEP.0000000000000333. https://pubmed.ncbi.nlm.nih.gov/36939197/

3. Ma, Xi, Zhang, Heyu, Yuan, Lan, Thacker, Phil, Li, Defa. . CREBL2, interacting with CREB, induces adipogenesis in 3T3-L1 adipocytes. In The Biochemical journal, 439, 27-38. doi:10.1042/BJ20101475. https://pubmed.ncbi.nlm.nih.gov/21728997/

4. Li, Shiying, Wu, Wenshuang, Zhang, Jing, Wu, Yumeng, Wang, Xinghui. 2023. Regulation of Schwann cell proliferation and migration via miR-195-5p-induced Crebl2 downregulation upon peripheral nerve damage. In Frontiers in cellular neuroscience, 17, 1173086. doi:10.3389/fncel.2023.1173086. https://pubmed.ncbi.nlm.nih.gov/37469605/