{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Integrin beta6 (ITGB6), which pairs with αv to form the heterodimer αvβ6, is emerging as a critical regulator of transforming growth factor–β (TGF‐β) activation in diverse tissues. In the lung, αvβ6 mediates the conversion of latent TGF‐β into its active form, thereby maintaining alveolar homeostasis; loss of ITGB6 has been shown to elevate macrophage matrix metalloproteinase‐12 expression and promote age‐dependent emphysema and exacerbate acute lung injury via dysregulated TGF‐β activation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond pulmonary biology, ITGB6 is de novo expressed on activated epithelial cells in injured tissues, where it modulates TGF‐β signaling in wound re‐epithelialization and liver fibrogenesis. For instance, in liver fibrosis, upregulated αvβ6 on bile duct epithelia and transitional hepatocytes contributes to extracellular matrix remodeling, and pharmacological inhibition of ITGB6 can induce antifibrotic and matrix‐degrading responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of cancer, ITGB6 has been implicated in tumor progression. Activation of STAT3 can transcriptionally upregulate ITGB6 and its ligand fibronectin, thereby enhancing cellular migration and invasion in cancers such as prostate carcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", while in oral squamous cell carcinoma ITGB6 signaling—through interaction with kinases like Fyn and subsequent MAPK pathway activation—promotes matrix metalloproteinase‐3 expression and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, genetic studies have identified susceptibility variants near ITGB6 that are associated with type 2 diabetes risk, possibly through effects on fasting glucose and insulin resistance"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", and with inflammatory bowel disease, indicating a broader role for ITGB6 in modulating inflammatory responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, during cutaneous wound healing, transcription factors such as FOXO1 regulate TGF‐β1 production and downstream targets including ITGB6, underlining its importance in keratinocyte migration and protection against oxidative stress during re‐epithelialization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore that ITGB6, primarily through its role in TGF‐β activation, is pivotal in controlling tissue homeostasis, repair, fibrosis, and cancer progression. Its dysregulation can predispose to chronic lung disease, fibrotic disorders, and tumor metastasis, while genetic variation near ITGB6 may contribute to susceptibility to metabolic and inflammatory diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "David G Morris, Xiaozhu Huang, Naftali Kaminski, et al. 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