Role of TGF-β3 in modulating inflammatory responses and wound healing processes in ischemic ulcers in atherosclerotic patients

Abstract

Ischemic ulcers pose a multifaceted clinical dilemma for patients with atherosclerosis, frequently compounded by suboptimal wound healing mechanisms. The dual function of Transforming Growth Factor Beta 3 (TGF-β3) in ischemic ulcer healing is not fully comprehended, despite its involvement in modulating inflammatory responses and tissue regeneration. The main aim of this investigation was to clarify the functions and mechanisms by which TGF-β3 regulates inflammatory responses and promotes wound healing in patients with ischemic ulcers who have atherosclerosis. Between August 2022 and November 2023, this cross-sectional investigation was conducted on 428 patients diagnosed with atherosclerotic ischemic ulcers in Haikou, China. The expression and function of TGF-β3 were examined throughout the different stages of wound healing, including inflammation, proliferation and remodelling. In addition to documenting patient demographics and ulcer characteristics, an analysis was conducted on biopsy samples to determine the expression of TGF-β3, pro-inflammatory and anti-inflammatory markers. A subset of patients were administered topical TGF-β3 in order to evaluate its therapeutic effects. The expression pattern of TGF-β3 was found to be stage-dependent and significant, exhibiting increased levels during the phase of inflammation and reduced activity in subsequent phases. TGF-β3 levels were found to be greater in ulcers that were larger and deeper, especially in inflammatory phase. TGF-β3 applied topically induced discernible enhancement in ulcer healing parameters, such as reduction in ulcer depth and size. The therapeutic significance of TGF-β3 was emphasised due to its twofold function of regulating the inflammatory environment and facilitating the regeneration of damaged tissues. Ischemic ulcer lesion healing is significantly influenced by TGF-β3, which functions as an anti-inflammatory and pro-inflammatory mediator. Its correlation with ulcer characteristics and stages of healing suggests that it may have utility as a targeted therapeutic agent.

Keywords: TGF-β3; atherosclerosis; foot ulcers; ischemic ulcers; wound healing.

FIGURE 1

Correlation of Transforming Growth Factor Beta 3 (TGF‐β3) levels with ulcer characteristics across healing phases. (A) Size of ulcer and TGF‐β3. (B) Depth of ulcer and TGF‐β3. (C) Duration of ulcer and TGF‐β3.