{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T12:16:47Z","timestamp":1771417007943,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2025M773132"],"award-info":[{"award-number":["2025M773132"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Glutamine (Gln), one of the most abundant free conditionally essential amino acids in animals, plays a pivotal role in protein and energy metabolism. Beyond its nutritional importance, Gln also modulates key cellular processes through diverse signaling pathways. Our previous studies have shown that appropriate Gln (0.4%) can promote collagen deposition in the swim bladder of Nibea coibor; however, the mechanism has not been investigated. Therefore, this study used transcriptomic analysis on the control group (0.0% Gln) and the 0.4% Gln group to screen for possible pathways and validate the function of candidate pathways in vitro. The results showed that the TGF-\u03b2\/Smads pathway was significantly upregulated in the 0.4% Gln group compared with 0.0% Gln. At the same time, Gln could also promote the swim bladder cells\u2019 proliferation and increase the extracellular type I collagen content and gene expression (col1a1, col1a2) in vitro, accompanied by the activation of the TGF-\u03b2\/Smads pathway (tgf-\u03b2, smad2, smad3, smad4 upregulated). Inhibition of the TGF-\u03b2\/Smads pathway (tgf-\u03b2, smad2, smad3, smad4 downregulated) partially reversed the effect of Gln on collagen deposition (col1a1, col1a2 downregulated), thus proving that the TGF-\u03b2\/Smads pathway is involved in the process of Gln on collagen deposition. In conclusion, the discovery not only expands our understanding of amino acid functions but establishes a foundational theory for further research on collagen regulation in fish.<\/jats:p>","DOI":"10.3390\/ani16040652","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T11:45:58Z","timestamp":1771415158000},"page":"652","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glutamine Promotes Collagen Deposition via TGF-\u03b2\/Smads Pathway in Swim Bladder of Chu\u2019s Croaker (Nibea coibor)"],"prefix":"10.3390","volume":"16","author":[{"given":"Yongjun","family":"Liang","sequence":"first","affiliation":[{"name":"College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China"},{"name":"Nansha-South China Agricultural University Fishery Research Institute, Guangzhou 511457, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haoyu","family":"Tian","sequence":"additional","affiliation":[{"name":"College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lanfei","family":"Xiao","sequence":"additional","affiliation":[{"name":"College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China"},{"name":"Nansha-South China Agricultural University Fishery Research Institute, Guangzhou 511457, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.matbio.2024.07.003","article-title":"Metabolic control of collagen synthesis","volume":"133","author":"Guillard","year":"2024","journal-title":"Matrix Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7015","DOI":"10.1002\/anie.200601432","article-title":"Photocontrolled folding and unfolding of a collagen triple helix","volume":"45","author":"Kusebauch","year":"2006","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_3","first-page":"a004978","article-title":"The collagen family","volume":"3","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.gep.2015.07.004","article-title":"Collagen duplicate genes of bone and cartilage participate during regeneration of zebrafish fin skeleton","volume":"19","author":"Duran","year":"2015","journal-title":"Gene Expr. Patterns"},{"key":"ref_5","first-page":"1468","article-title":"A novel enzymatic method for preparation and characterization of collagen film from swim bladder of fish rohu (Labeo rohita)","volume":"6","author":"Sripriya","year":"2015","journal-title":"Food Nutr. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.molcel.2012.05.043","article-title":"Glutaminolysis activates rag-mTORC1 signaling","volume":"47","author":"Oppliger","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"24795","DOI":"10.1021\/acs.jafc.5c08836","article-title":"Inhibition of autophagy is involved in the collagen deposition promoted by dietary leucin in chu\u2019s croaker (Nibea coibor)","volume":"73","author":"Liu","year":"2025","journal-title":"J. Agric. Food Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"102078","DOI":"10.1016\/j.tranon.2024.102078","article-title":"Glutamine withdrawal leads to the preferential activation of lipid metabolism in metastatic colorectal cancer","volume":"48","author":"Eylem","year":"2024","journal-title":"Transl. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1165\/rcmb.2019-0008OC","article-title":"Glutamine metabolism is required for collagen protein synthesis in lung fibroblasts","volume":"61","author":"Hamanaka","year":"2019","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1007\/s00726-020-02851-2","article-title":"Nutrition and metabolism of glutamate and glutamine in fish","volume":"52","author":"Li","year":"2020","journal-title":"Amino Acids"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.cbpa.2015.09.012","article-title":"Dietary glutamine supplementation effects on amino acid metabolism, intestinal nutrient absorption capacity and antioxidant response of gilthead sea bream (Sparus aurata) juveniles","volume":"191","author":"Coutinho","year":"2016","journal-title":"Comp. Biochem. Phys. A"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103140","DOI":"10.1016\/j.aqrep.2025.103140","article-title":"Effects of dietary glutamine on growth performance, antioxidant capacity, and swim bladder collagen deposition in chu\u2019s croaker (Nibea coibor)","volume":"45","author":"Tian","year":"2025","journal-title":"Aquac. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wang, R.Y., Yuan, X., Xie, T., Zhao, X., Li, J.Y., Zhang, X.H., and Lv, C.Z. (2025). The endogenous glutamatergic transmitter system promotes collagen synthesis in cardiac fibroblasts under hypoxia. Front. Cardiovasc. Med., 12.","DOI":"10.3389\/fcvm.2025.1638650"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/s41392-024-01764-w","article-title":"TGF-\u03b2 signaling in health, disease, and therapeutics","volume":"9","author":"Deng","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"738360","DOI":"10.1016\/j.aquaculture.2022.738360","article-title":"The transforming growth factor beta (TGF-\u03b2\/Smads) pathway regulates collagen synthesis and deposition in swim bladder of Chu\u2019s croaker (Nibea coibor) stimulated by proline","volume":"558","author":"Rong","year":"2022","journal-title":"Aquaculture"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1007\/s10695-021-00941-w","article-title":"Both TGF-\u03b21 and Smad4 regulate type I collagen expression in the muscle of grass carp, Ctenopharyngodon Idella","volume":"47","author":"Xia","year":"2021","journal-title":"Fish Physio Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"738976","DOI":"10.1016\/j.aquaculture.2022.738976","article-title":"Dietary glutamine improves growth and intestinal morphology of juvenile GIFT tilapia (Oreochromis niloticus) but has limited effects on innate immunity and antioxidant capacity","volume":"536","author":"Carvalho","year":"2023","journal-title":"Aquaculture"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1002\/jcb.20605","article-title":"Diverse biological functions of extracellular collagen processing enzymes","volume":"96","author":"Trackman","year":"2005","journal-title":"J. Cell. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"100306","DOI":"10.1016\/j.fochms.2025.100306","article-title":"Role of timp2 in Ctenopharyngodon idellus muscle collagen deposition and the regulatory mechanism by Cu2+","volume":"11","author":"Lin","year":"2025","journal-title":"Food Chem. Mol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s12562-011-0443-7","article-title":"Molecular species of collagen in muscular and vertebral parts of white sturgeon Acipenser transmontanus","volume":"78","author":"Mizuta","year":"2012","journal-title":"Fish. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s40104-022-00747-7","article-title":"Dietary protein levels changed the hardness of muscle by acting on muscle fiber growth and the metabolism of collagen in sub-adult grass carp (Ctenopharyngodon idella)","volume":"13","author":"Dong","year":"2022","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zhu, L., Yu, H., Liu, S.Y., Xiao, X.S., Dong, W.H., Chen, Y.N., Xu, W., and Zhu, T. (2015). Prognostic value of tissue inhibitor of metalloproteinase-2 expression in patients with non-small cell lung cancer: A systematic review and meta-analysis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124230"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Li, L.Y., Zhao, Y.Q., He, H., Chi, C.F., and Wang, B. (2018). Physicochemical and antioxidant properties of acid- and pepsin-soluble collagens from the scales of miiuy croaker (Miichthys Miiuy). Mar. Drugs, 16.","DOI":"10.3390\/md16100394"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Dong, H.B., Chen, J.W., Li, Y.J., Wang, C., Jiao, C.Y., and Wang, L.Q. (2024). Influence of liquid nitrogen pre-freezing and drying methods on the collagen content, physical properties, and flavor of fish swim bladder. Foods, 13.","DOI":"10.3390\/foods13172790"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4167","DOI":"10.1073\/pnas.83.12.4167","article-title":"Transforming growth factor type beta: Rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro","volume":"83","author":"Roberts","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/nrrheum.2009.26","article-title":"Transforming growth factor beta as a therapeutic target in systemic sclerosis","volume":"5","author":"Varga","year":"2009","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"100705","DOI":"10.1016\/j.repbio.2022.100705","article-title":"TGF-\u03b21 induces type I collagen deposition in granulosa cells via the AKT\/GSK-3\u03b2 signaling pathway-mediated MMP1 down-regulation","volume":"22","author":"Shen","year":"2022","journal-title":"Reprod. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1152\/japplphysiol.00463.2006","article-title":"TGF-\u03b21 and TNF-\u03b1 are involved in the transcription of type I collagen \u03b12 gene in soleus muscle atrophied by mechanical unloading","volume":"104","author":"Hirose","year":"2008","journal-title":"J. Appl. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/nature02006","article-title":"Smad-dependent and Smad-independent pathways in TGF-\u03b2 family signalling","volume":"425","author":"Derynck","year":"2003","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1111\/ajd.12126","article-title":"Daidzein stimulates collagen synthesis by activating the TGF-\u03b2\/smad signal pathway","volume":"56","author":"Zhao","year":"2015","journal-title":"Australas. J. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.gene.2018.10.074","article-title":"Smad4-dependent regulation of type I collagen expression in the muscle of grass carp fed with faba bean","volume":"685","author":"Yu","year":"2019","journal-title":"Gene"}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/4\/652\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T11:56:30Z","timestamp":1771415790000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/4\/652"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,18]]},"references-count":31,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ani16040652"],"URL":"https:\/\/doi.org\/10.3390\/ani16040652","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,18]]}}}