**6.2 Proteoglycans**

*Tendons*

**Figure 5.**

**48**

active TGF-β can be released of ECM through mechanical force or by matrix proteolytic enzymes as ADAMTS1, MMP-2, and MMP-9 [75]. In the case of mechanical force-mediated TGF-β activation, αvβ6 integrin, transmembrane proteins that connect intracellular cytoskeleton proteins together with ECM, suffers a conformational change that signals to liberate latent TGF-β; now matrix biologically active to binding in surface receptors are found in ECM cell. The binding between ligand (TGF-β) and their receptor permits activation of downstream intracellular signaling pathways, responsible for gene transcription, essential to ECM remodeling (for

Interestingly, Heinemeyer et al. [77] confirmed in their study that TGF-β could be involved in collagen I and collagen III regulations in different types of training (concentric, eccentric, or isometric). Following 24 hours post training, a TGF-β increased gene expression in all types of training (concentric, eccentric, or isometric) with no difference among training types was noticed. These results are in accordance with previous studies that showed eccentric training is also accompanied by fibroblast proliferation, main cells responsible for synthesizing collagen in

About ECM, connective tissue growth factor (CTGF), downstream mediator of TGF-β, in fibroblastic cells, also seems to be responsible for tendon ECM remodeling by exercise. It was noticed in human patellar tendon submitted to 1 hour of unilateral kicking exercise (workload of 67%) with frequency of 35 kicks per min and 2100 concentric contractions that CTGF gene expression total volume was increased, together with COL1A1 mRNA levels, 24 hours postexercise. On the other

instance, collagen, MMPs, and TIMPs) (**Figure 5**) [75].

*Overview of TGF-β signaling pathways. Adapted from Gumucio et al. [75].*

response to exercise [81, 82].

Other molecules, such as proteoglycans, are essential for fibrillogenesis regulation and tendon structure maintenance [84]. The proteoglycan regulation from exercise is still not clear on the literature, whereas most studies have observed the exercise effects over collagen and some growth factors responsible for gene expression of those molecules. However, it seems that resistance exercise appears not to induce changes in proteoglycan gene regulation. In the previous study, there were no observed changes in mRNA expression of the proteoglycans: decorin, biglycan, fibromodulin, and versican from resting levels at 4 or 24 hours after resistance training that corresponded to workload of 70% of the subject's concentric maximum repetition [84]. Although, this study hasn't found changes between proteoglycans, it is possible to infer that the regulation of these molecules could be related to mode, duration, and intensity of the exercise.
